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For: Bodd M, Ráki M, Tollefsen S, Fallang LE, Bergseng E, Lundin KEA, Sollid LM. HLA-DQ2-restricted gluten-reactive T cells produce IL-21 but not IL-17 or IL-22. Mucosal Immunol 2010;3:594-601. [PMID: 20571486 DOI: 10.1038/mi.2010.36] [Citation(s) in RCA: 111] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]

For:	Bodd M, Ráki M, Tollefsen S, Fallang LE, Bergseng E, Lundin KEA, Sollid LM. HLA-DQ2-restricted gluten-reactive T cells produce IL-21 but not IL-17 or IL-22. Mucosal Immunol 2010;3:594-601. [PMID: 20571486 DOI: 10.1038/mi.2010.36] [Citation(s) in RCA: 111] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]

Number

Cited by Other Article(s)

Slager J, Simpson HL, Gacesa R, Chen L, Tan IL, Gelderloos J, Maatman A, Wijmenga C, Zhernakova A, Fu J, Weersma RK, Gonera G, Jonkers IH, Withoff S. High-resolution analysis of the treated coeliac disease microbiome reveals strain-level variation. Gut Microbes 2025;17:2489071. [PMID: 40289251 PMCID: PMC12036492 DOI: 10.1080/19490976.2025.2489071] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2024] [Revised: 03/05/2025] [Accepted: 03/31/2025] [Indexed: 04/30/2025] Open

Abstract

BACKGROUND

Coeliac disease (CeD) is an immune-mediated disorder primarily affecting the small intestine, characterized by an inflammatory immune reaction to dietary gluten. CeD onset results from a multifaceted interplay of genetic and environmental factors. While recent data show that alterations in gut microbiome composition could play an important role, many current studies are constrained by small sample sizes and limited resolution.

METHODS

To address these limitations, we analyzed fecal gut microbiota from two Dutch cohorts, CeDNN (128 treated CeD patients (tCeD), 106 controls) and the Lifelines Dutch Microbiome Project (24 self-reported tCeD, 654 controls), using shotgun metagenomic sequencing. Self-reported IBS (570 cases, 1710 controls) and IBD (93 cases, 465 controls) were used as comparative conditions of the gastrointestinal tract. Interindividual variation within the case and control groups was calculated at whole microbiome and strain level. Finally, species-specific gene repertoires were analyzed in tCeD patients and controls.

RESULTS

Within-individual microbiome diversity was decreased in patients with self-reported IBS and IBD but not in tCeD patients. Each condition displayed a unique microbial pattern and, in addition to confirming previously reported microbiome associations, we identify an increase in the levels of Clostridium sp. CAG:253, Roseburia hominis, and Eggerthella lenta, amongst others. We further show that the observed changes can partially be explained by gluten-free diet adherence. We also observe increased interindividual variation of gut microbiome composition among tCeD patients and a higher bacterial mutation frequency in tCeD that contributes to higher interindividual variation at strain level. In addition, the immotile European subspecies of Eubacterium rectale, which has a distinct carbohydrate metabolism potential, was nearly absent in tCeD patients.

CONCLUSION

Our study sheds light on the complex interplay between the gut microbiome and CeD, revealing increased interindividual variation and strain-level variation in tCeD patients. These findings expand our understanding of the microbiome's role in intestinal health and disease.

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Affiliation(s)

Jelle Slager Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
Hanna L. Simpson Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
Ranko Gacesa Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
Lianmin Chen Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands Department of Cardiology, Nanjing Medical University, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China Cardiovascular Research Center, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, China
Ineke L. Tan Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
Jody Gelderloos Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
Astrid Maatman Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
Cisca Wijmenga Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
Alexandra Zhernakova Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
Jingyuan Fu Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
Rinse K. Weersma Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
Gieneke Gonera Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands Department of Pediatrics, Wilhelmina Hospital Assen, Assen, The Netherlands
Iris H. Jonkers Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
Sebo Withoff Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

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FitzPatrick MEB, Antanaviciute A, Dunstan M, Künnapuu K, Trzupek D, Provine NM, Dooley K, Zhang JY, Irwin SL, Garner LC, Pernes JI, Ferreira RC, Sasson SC, Aschenbrenner D, Agarwal D, Rodrigues A, Howarth L, Brain O, Ruane D, Soilleux E, Teichmann SA, Dendrou CA, Simmons A, Uhlig HH, Todd JA, Klenerman P. Immune-epithelial-stromal networks define the cellular ecosystem of the small intestine in celiac disease. Nat Immunol 2025:10.1038/s41590-025-02146-2. [PMID: 40328997 DOI: 10.1038/s41590-025-02146-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2023] [Accepted: 03/25/2025] [Indexed: 05/08/2025]

Affiliation(s)

Michael E B FitzPatrick Translational Gastroenterology and Liver Unit, Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK.
Agne Antanaviciute MRC Translational Immune Discovery Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK MRC WIMM Centre for Computational Biology, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK
Melanie Dunstan Translational Gastroenterology and Liver Unit, Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK Centre for Human Genetics, Nuffield Department of Medicine, NIHR Biomedical Research Centres, University of Oxford, Oxford, UK
Karolina Künnapuu Translational Gastroenterology and Liver Unit, Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK
Dominik Trzupek Centre for Human Genetics, Nuffield Department of Medicine, NIHR Biomedical Research Centres, University of Oxford, Oxford, UK
Nicholas M Provine Translational Gastroenterology and Liver Unit, Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK Centre for Human Genetics, Nuffield Department of Medicine, NIHR Biomedical Research Centres, University of Oxford, Oxford, UK Pandemic Sciences Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK
Kyla Dooley Centre for Human Genetics, Nuffield Department of Medicine, NIHR Biomedical Research Centres, University of Oxford, Oxford, UK Pandemic Sciences Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK
Jia-Yuan Zhang MRC WIMM Centre for Computational Biology, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK
Sophie L Irwin Division of Infectious Diseases, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA
Lucy C Garner Translational Gastroenterology and Liver Unit, Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK
Jane I Pernes Centre for Human Genetics, Nuffield Department of Medicine, NIHR Biomedical Research Centres, University of Oxford, Oxford, UK
Ricardo C Ferreira Centre for Human Genetics, Nuffield Department of Medicine, NIHR Biomedical Research Centres, University of Oxford, Oxford, UK
Sarah C Sasson Kirby Institute, University of New South Wales, Sydney, New South Wales, Australia
Dominik Aschenbrenner Immunology Disease Area, Novartis BioMedical Research, Basel, Switzerland
Devika Agarwal Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK
Astor Rodrigues University Children's Hospital, John Radcliffe Hospital, Oxford, UK
Lucy Howarth University Children's Hospital, John Radcliffe Hospital, Oxford, UK
Oliver Brain Translational Gastroenterology and Liver Unit, Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK
Darren Ruane Janssen Research & Development, Immunology Translational Sciences and Medicine, La Jolla, CA, USA
Elizabeth Soilleux Department of Pathology, University of Cambridge, Cambridge, UK
Sarah A Teichmann Wellcome Sanger Institute, University of Cambridge, Cambridge, UK
Calliope A Dendrou Centre for Human Genetics, Nuffield Department of Medicine, NIHR Biomedical Research Centres, University of Oxford, Oxford, UK Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK
Alison Simmons Translational Gastroenterology and Liver Unit, Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK MRC Translational Immune Discovery Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK
Holm H Uhlig Translational Gastroenterology and Liver Unit, Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK Centre for Human Genetics, Nuffield Department of Medicine, NIHR Biomedical Research Centres, University of Oxford, Oxford, UK University Children's Hospital, John Radcliffe Hospital, Oxford, UK NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK
John A Todd Centre for Human Genetics, Nuffield Department of Medicine, NIHR Biomedical Research Centres, University of Oxford, Oxford, UK
Paul Klenerman Translational Gastroenterology and Liver Unit, Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, Oxford, UK

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Santonicola A, Soldaini C, Ciacci C. New therapies in celiac disease. Curr Opin Gastroenterol 2025;41:124-131. [PMID: 39862215 PMCID: PMC11970589 DOI: 10.1097/mog.0000000000001080] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/27/2025]

Kowalski MK, Domżał-Magrowska D, Małecka-Wojciesko E. Celiac Disease-Narrative Review on Progress in Celiac Disease. Foods 2025;14:959. [PMID: 40231983 PMCID: PMC11941517 DOI: 10.3390/foods14060959] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2025] [Revised: 02/28/2025] [Accepted: 03/09/2025] [Indexed: 04/16/2025] Open

Abstract

Celiac disease is defined as a systemic immunological disorder caused by gluten (gliadin and other prolamin) in genetically predisposed individuals, who present with a variety of gluten-dependent symptoms, specific antibodies, the presence of the HLA DQ2 and DQ8 histocompatibility antigen, and enteropathy. Its prevalence, depending on the studied population and methodology, is estimated at 0.75-1.6% of the general population. During the complex immune reaction it induces, most cells involved in inflammatory processes are activated, which leads to the gradual atrophy of intestinal villi and the proliferation of enterocytes within intestinal crypts. The pathogenesis of celiac disease is extremely complicated and is still the subject of research. According to the current diagnostic guidelines, the following criteria should be taken into account: clinical symptoms (intestinal and extraintestinal), the presence of antibodies against tissue transglutaminase in the IgA class, the level of total IgA, and the presence of typical histological changes in duodenal biopsies. Diet-resistant celiac disease is one of the most important clinical challenges, causing serious complications. Currently, the basic method for treating celiac disease is an elimination diet (i.e., the exclusion of products that may contain gluten from the diet), however, new therapeutic strategies are still being sought, mainly based on supplementation with exogenous endopeptidases, modification of the immune response, and the use of zonulin inhibitors and transglutaminase 2 inhibitors. Clinical trials of new drugs are ongoing. The gradually expanding knowledge about the pathogenesis of celiac disease may allow for the development of new therapeutic strategies for both patients with a mild disease course, as well as those that are diet-resistant.

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Ge HJ, Chen XL. Advances in understanding and managing celiac disease: Pathophysiology and treatment strategies. World J Gastroenterol 2024;30:3932-3941. [PMID: 39351055 PMCID: PMC11438662 DOI: 10.3748/wjg.v30.i35.3932] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2024] [Revised: 08/12/2024] [Accepted: 08/26/2024] [Indexed: 09/13/2024] Open

Abadie V, Han AS, Jabri B, Sollid LM. New Insights on Genes, Gluten, and Immunopathogenesis of Celiac Disease. Gastroenterology 2024;167:4-22. [PMID: 38670280 PMCID: PMC11283582 DOI: 10.1053/j.gastro.2024.03.042] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2023] [Revised: 03/10/2024] [Accepted: 03/11/2024] [Indexed: 04/28/2024]

Volta U, Rostami K, Auricchio R, Lundin KEA. Diagnosis of Seronegative and Ultrashort Celiac Disease. Gastroenterology 2024;167:104-115. [PMID: 38286391 DOI: 10.1053/j.gastro.2024.01.029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/24/2023] [Revised: 12/19/2023] [Accepted: 01/04/2024] [Indexed: 01/31/2024]

Ye L, Zheng W, Li X, Han W, Shen J, Lin Q, Hou L, Liao L, Zeng X. The Role of Gluten in Food Products and Dietary Restriction: Exploring the Potential for Restoring Immune Tolerance. Foods 2023;12:4179. [PMID: 38002235 PMCID: PMC10670377 DOI: 10.3390/foods12224179] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2023] [Revised: 11/16/2023] [Accepted: 11/17/2023] [Indexed: 11/26/2023] Open

Affiliation(s)

Li Ye Guangdong Key Laboratory of Intelligent Food Manufacturing, Foshan University, Foshan 528225, China; (L.Y.); (W.Z.); (X.L.); (W.H.); (J.S.); (Q.L.); (L.H.) Department of Food Science, Foshan University, Foshan 528000, China
Wenyu Zheng Guangdong Key Laboratory of Intelligent Food Manufacturing, Foshan University, Foshan 528225, China; (L.Y.); (W.Z.); (X.L.); (W.H.); (J.S.); (Q.L.); (L.H.) Department of Food Science, Foshan University, Foshan 528000, China School of Food Science and Engineering, South China University of Technology, Guangzhou 510640, China
Xue Li Guangdong Key Laboratory of Intelligent Food Manufacturing, Foshan University, Foshan 528225, China; (L.Y.); (W.Z.); (X.L.); (W.H.); (J.S.); (Q.L.); (L.H.) Department of Food Science, Foshan University, Foshan 528000, China
Wenmin Han Guangdong Key Laboratory of Intelligent Food Manufacturing, Foshan University, Foshan 528225, China; (L.Y.); (W.Z.); (X.L.); (W.H.); (J.S.); (Q.L.); (L.H.) Department of Food Science, Foshan University, Foshan 528000, China
Jialing Shen Guangdong Key Laboratory of Intelligent Food Manufacturing, Foshan University, Foshan 528225, China; (L.Y.); (W.Z.); (X.L.); (W.H.); (J.S.); (Q.L.); (L.H.) Department of Food Science, Foshan University, Foshan 528000, China
Qiuya Lin Guangdong Key Laboratory of Intelligent Food Manufacturing, Foshan University, Foshan 528225, China; (L.Y.); (W.Z.); (X.L.); (W.H.); (J.S.); (Q.L.); (L.H.) Department of Food Science, Foshan University, Foshan 528000, China
Liyan Hou Guangdong Key Laboratory of Intelligent Food Manufacturing, Foshan University, Foshan 528225, China; (L.Y.); (W.Z.); (X.L.); (W.H.); (J.S.); (Q.L.); (L.H.) Department of Food Science, Foshan University, Foshan 528000, China
Lan Liao Guangdong Key Laboratory of Intelligent Food Manufacturing, Foshan University, Foshan 528225, China; (L.Y.); (W.Z.); (X.L.); (W.H.); (J.S.); (Q.L.); (L.H.) Department of Food Science, Foshan University, Foshan 528000, China
Xin’an Zeng Guangdong Key Laboratory of Intelligent Food Manufacturing, Foshan University, Foshan 528225, China; (L.Y.); (W.Z.); (X.L.); (W.H.); (J.S.); (Q.L.); (L.H.) Department of Food Science, Foshan University, Foshan 528000, China School of Food Science and Engineering, South China University of Technology, Guangzhou 510640, China

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Patt YS, Lahat A, David P, Patt C, Eyade R, Sharif K. Unraveling the Immunopathological Landscape of Celiac Disease: A Comprehensive Review. Int J Mol Sci 2023;24:15482. [PMID: 37895160 PMCID: PMC10607730 DOI: 10.3390/ijms242015482] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2023] [Revised: 10/20/2023] [Accepted: 10/21/2023] [Indexed: 10/29/2023] Open

Strohmeier V, Andrieux G, Unger S, Pascual-Reguant A, Klocperk A, Seidl M, Marques OC, Eckert M, Gräwe K, Shabani M, von Spee-Mayer C, Friedmann D, Harder I, Gutenberger S, Keller B, Proietti M, Bulashevska A, Grimbacher B, Provaznik J, Benes V, Goldacker S, Schell C, Hauser AE, Boerries M, Hasselblatt P, Warnatz K. Interferon-Driven Immune Dysregulation in Common Variable Immunodeficiency-Associated Villous Atrophy and Norovirus Infection. J Clin Immunol 2023;43:371-390. [PMID: 36282455 PMCID: PMC9892141 DOI: 10.1007/s10875-022-01379-2] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2022] [Accepted: 10/03/2022] [Indexed: 02/07/2023]

Affiliation(s)

Valentina Strohmeier Department of Rheumatology and Clinical Immunology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany Center for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany Faculty of Biology, University of Freiburg, Freiburg, Germany
Geoffroy Andrieux Institute of Medical Bioinformatics and Systems Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
Susanne Unger Department of Rheumatology and Clinical Immunology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany Center for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
Anna Pascual-Reguant Department of Rheumatology and Clinical Immunology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität Zu Berlin, Charitéplatz 1, 10117, Berlin, Germany Immune Dynamics, Deutsches Rheuma-Forschungszentrum (DRFZ), a Leibniz Institute, Charitéplatz 1, 10117, Berlin, Germany
Adam Klocperk Department of Rheumatology and Clinical Immunology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany Center for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany Department of Immunology, 2Nd Faculty of Medicine, Charles University and University Hospital in Motol, Prague, Czech Republic
Maximilian Seidl Institute for Surgical Pathology, University Medical Center Freiburg, Freiburg, Germany Institute of Pathology, Heinrich Heine University and University Hospital of Dusseldorf, Dusseldorf, Germany
Otavio Cabral Marques Department of Rheumatology and Clinical Immunology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany Center for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, SP, Brazil Network of Immunity in Infection, Malignancy, and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), São Paulo, SP, Brazil Department of Pharmacy and Postgraduate Program of Health and Science, Federal University of Rio Grande do Norte, Natal, Brazil
Marleen Eckert Department of Rheumatology and Clinical Immunology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany Center for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany Faculty of Biology, University of Freiburg, Freiburg, Germany
Katja Gräwe Institute for Surgical Pathology, University Medical Center Freiburg, Freiburg, Germany
Michelle Shabani Institute for Surgical Pathology, University Medical Center Freiburg, Freiburg, Germany
Caroline von Spee-Mayer Department of Rheumatology and Clinical Immunology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany Center for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
David Friedmann Department of Rheumatology and Clinical Immunology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany Center for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany Faculty of Biology, University of Freiburg, Freiburg, Germany
Ina Harder Department of Rheumatology and Clinical Immunology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany Center for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
Sylvia Gutenberger Department of Rheumatology and Clinical Immunology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany Center for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
Baerbel Keller Department of Rheumatology and Clinical Immunology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany Center for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
Michele Proietti Center for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany RESIST - Cluster of Excellence 2155 to Hanover Medical School, Satellite Center Freiburg, Freiburg, Germany
Alla Bulashevska Department of Rheumatology and Clinical Immunology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany Center for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
Bodo Grimbacher Department of Rheumatology and Clinical Immunology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany Center for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany RESIST - Cluster of Excellence 2155 to Hanover Medical School, Satellite Center Freiburg, Freiburg, Germany DZIF - German Center for Infection Research, Satellite Center Freiburg, Freiburg, Germany CIBSS - Centre for Integrative Biological Signalling Studies, Albert-Ludwigs University, Freiburg, Germany
Jan Provaznik European Molecular Biology Laboratory (EMBL), Genomics Core Facility, Heidelberg, Germany
Vladimir Benes European Molecular Biology Laboratory (EMBL), Genomics Core Facility, Heidelberg, Germany
Sigune Goldacker Department of Rheumatology and Clinical Immunology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany Center for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
Christoph Schell Institute for Surgical Pathology, University Medical Center Freiburg, Freiburg, Germany
Anja E Hauser Department of Rheumatology and Clinical Immunology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität Zu Berlin, Charitéplatz 1, 10117, Berlin, Germany Immune Dynamics, Deutsches Rheuma-Forschungszentrum (DRFZ), a Leibniz Institute, Charitéplatz 1, 10117, Berlin, Germany
Melanie Boerries Institute of Medical Bioinformatics and Systems Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Partner Site Freiburg, 79110, Freiburg, Germany
Peter Hasselblatt Department of Medicine II, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
Klaus Warnatz Department of Rheumatology and Clinical Immunology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany. Center for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

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Iversen R, Sollid LM. The Immunobiology and Pathogenesis of Celiac Disease. ANNUAL REVIEW OF PATHOLOGY 2023;18:47-70. [PMID: 36067801 DOI: 10.1146/annurev-pathmechdis-031521-032634] [Citation(s) in RCA: 94] [Impact Index Per Article: 47.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]

Skoracka K, Hryhorowicz S, Rychter AM, Ratajczak AE, Szymczak-Tomczak A, Zawada A, Słomski R, Dobrowolska A, Krela-Kaźmierczak I. Why are western diet and western lifestyle pro-inflammatory risk factors of celiac disease? Front Nutr 2023;9:1054089. [PMID: 36742009 PMCID: PMC9895111 DOI: 10.3389/fnut.2022.1054089] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2022] [Accepted: 12/31/2022] [Indexed: 01/21/2023] Open

Mamone G, Di Stasio L, Vitale S, Picascia S, Gianfrani C. Analytical and functional approaches to assess the immunogenicity of gluten proteins. Front Nutr 2023;9:1049623. [PMID: 36741992 PMCID: PMC9890883 DOI: 10.3389/fnut.2022.1049623] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2022] [Accepted: 12/15/2022] [Indexed: 01/19/2023] Open

Earley ZM, Lisicka W, Sifakis JJ, Aguirre-Gamboa R, Kowalczyk A, Barlow JT, Shaw DG, Discepolo V, Tan IL, Gona S, Ernest JD, Matzinger P, Barreiro LB, Morgun A, Bendelac A, Ismagilov RF, Shulzhenko N, Riesenfeld SJ, Jabri B. GATA4 controls regionalization of tissue immunity and commensal-driven immunopathology. Immunity 2023;56:43-57.e10. [PMID: 36630917 PMCID: PMC10262782 DOI: 10.1016/j.immuni.2022.12.009] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2022] [Revised: 11/16/2022] [Accepted: 12/12/2022] [Indexed: 01/12/2023]

Affiliation(s)

Zachary M Earley Committee on Immunology, University of Chicago, Chicago, IL, USA; Department of Medicine, University of Chicago, Chicago, IL, USA
Wioletta Lisicka Committee on Immunology, University of Chicago, Chicago, IL, USA; Department of Medicine, University of Chicago, Chicago, IL, USA
Joseph J Sifakis Department of Chemistry, University of Chicago, Chicago, IL, USA
Raúl Aguirre-Gamboa Department of Medicine, University of Chicago, Chicago, IL, USA
Anita Kowalczyk Department of Medicine, University of Chicago, Chicago, IL, USA
Jacob T Barlow Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA
Dustin G Shaw Committee on Immunology, University of Chicago, Chicago, IL, USA; Department of Medicine, University of Chicago, Chicago, IL, USA
Valentina Discepolo Department of Medical Translational Sciences and European Laboratory for the Investigation of Food Induced Diseases, University of Federico II, Naples, Italy
Ineke L Tan Department of Gastroenterology and Hepatology, University of Groningen and University of Medical Center Groningen, Groningen, the Netherlands
Saideep Gona Genetics, Genomics, and Systems Biology, University of Chicago, Chicago, IL, USA
Jordan D Ernest Department of Medicine, University of Chicago, Chicago, IL, USA
Polly Matzinger Ghost Lab, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
Luis B Barreiro Committee on Immunology, University of Chicago, Chicago, IL, USA; Department of Medicine, University of Chicago, Chicago, IL, USA; Genetics, Genomics, and Systems Biology, University of Chicago, Chicago, IL, USA
Andrey Morgun College of Pharmacy, Oregon State University, Corvallis, OR, USA
Albert Bendelac Committee on Immunology, University of Chicago, Chicago, IL, USA; Department of Pathology, University of Chicago, Chicago, IL, USA
Rustem F Ismagilov Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA; Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA, USA
Natalia Shulzhenko Department of Biomedical Sciences, Oregon State University, Corvallis, OR, USA
Samantha J Riesenfeld Committee on Immunology, University of Chicago, Chicago, IL, USA; Department of Medicine, University of Chicago, Chicago, IL, USA; Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL, USA; Institute for Biophysical Dynamics, University of Chicago, Chicago, IL, USA.
Bana Jabri Committee on Immunology, University of Chicago, Chicago, IL, USA; Department of Medicine, University of Chicago, Chicago, IL, USA; Department of Pathology, University of Chicago, Chicago, IL, USA; Department of Pediatrics, University of Chicago, Chicago, IL, USA.

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Abadie V, Khosla C, Jabri B. A Mouse Model of Celiac Disease. Curr Protoc 2022;2:e515. [PMID: 35994521 PMCID: PMC10203737 DOI: 10.1002/cpz1.515] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/25/2023]

Abstract

The design and use of mouse models that reproduce key features of human diseases are critical to advance our understanding of the pathogenesis of autoimmune diseases and to test new therapeutic strategies. Celiac disease is a unique organ-specific autoimmune-like disorder occurring in genetically susceptible individuals carrying HLA-DQ2 or HLA-DQ8 molecules who consume gluten. The key histological characteristic of the disease in humans is the destruction of the lining of the small intestine, a feature that has been difficult to reproduce in immunocompetent animal models. This unit describes the DQ8-Dd -villin-IL-15 transgenic mouse model of CeD, which was engineered based on the knowledge acquired from studying CeD patients' intestinal samples, and which represents the first animal model that develops villous atrophy in an HLA- and gluten-dependent manner without administration of any adjuvant. We provide detailed protocols for inducing and monitoring intestinal tissue damage, evaluating the cytotoxic properties of intraepithelial lymphocytes that mediate enterocyte lysis, and assessing the activation of the enzyme transglutaminase 2, which contributes to the generation of highly immunogenic gluten peptides. Detailed protocols to prepare pepsin-trypsin digested gliadin (PT-gliadin) or chymotrypsin-digested gliadin (CT-gliadin), which allow antibody detection against native or deamidated gluten peptides, are also provided in this unit. © 2022 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Induction of celiac-like disease in DQ8-Dd -villin-IL-15tg mice Basic Protocol 2: Histological assessment of villous atrophy Support Protocol 1: Morphometric assessment of villous/crypt ratio Support Protocol 2: Evaluation of epithelial cells renewal Support Protocol 3: Evaluation of the density of intraepithelial lymphocytes Basic Protocol 3: Analysis of cytotoxic intraepithelial lymphocytes Basic Protocol 4: Transglutaminase 2 activation and measurement of antibodies against native and deamidated gluten peptides Support Protocol 4: Preparation of CT-gliadin Support Protocol 5: Preparation of PT-gliadin.

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Beneficial Role of Microbial Transglutaminase in the Pathogenetic Mechanisms of Coeliac Disease. J Pediatr Gastroenterol Nutr 2022;74:728-733. [PMID: 35442226 DOI: 10.1097/mpg.0000000000003451] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]

Liu C, Yang J. Enteric Glial Cells in Immunological Disorders of the Gut. Front Cell Neurosci 2022;16:895871. [PMID: 35573829 PMCID: PMC9095930 DOI: 10.3389/fncel.2022.895871] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2022] [Accepted: 04/07/2022] [Indexed: 11/13/2022] Open

Aboulaghras S, Piancatelli D, Oumhani K, Balahbib A, Bouyahya A, Taghzouti K. Pathophysiology and immunogenetics of celiac disease. Clin Chim Acta 2022;528:74-83. [PMID: 35120899 DOI: 10.1016/j.cca.2022.01.022] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2021] [Revised: 01/20/2022] [Accepted: 01/28/2022] [Indexed: 02/08/2023]

Stamnaes J. Insights from tissue "omics" analysis on intestinal remodeling in celiac disease. Proteomics 2021;21:e2100057. [PMID: 34633755 DOI: 10.1002/pmic.202100057] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Revised: 09/30/2021] [Accepted: 10/01/2021] [Indexed: 12/20/2022]

Yao Y, Wyrozżemski Ł, Lundin KEA, Sandve GK, Qiao SW. Differential expression profile of gluten-specific T cells identified by single-cell RNA-seq. PLoS One 2021;16:e0258029. [PMID: 34618841 PMCID: PMC8496852 DOI: 10.1371/journal.pone.0258029] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2020] [Accepted: 09/17/2021] [Indexed: 01/22/2023] Open

Lamas B, Hernandez-Galan L, Galipeau HJ, Constante M, Clarizio A, Jury J, Breyner NM, Caminero A, Rueda G, Hayes CL, McCarville JL, Bermudez Brito M, Planchais J, Rolhion N, Murray JA, Langella P, Loonen LMP, Wells JM, Bercik P, Sokol H, Verdu EF. Aryl hydrocarbon receptor ligand production by the gut microbiota is decreased in celiac disease leading to intestinal inflammation. Sci Transl Med 2021;12:12/566/eaba0624. [PMID: 33087499 DOI: 10.1126/scitranslmed.aba0624] [Citation(s) in RCA: 117] [Impact Index Per Article: 29.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2019] [Revised: 02/24/2020] [Accepted: 06/02/2020] [Indexed: 12/15/2022]

Affiliation(s)

Bruno Lamas Farncombe Family Digestive Health Research Institute, Department of Medicine, McMaster University, Hamilton, Ontario, Canada
Leticia Hernandez-Galan Farncombe Family Digestive Health Research Institute, Department of Medicine, McMaster University, Hamilton, Ontario, Canada
Heather J Galipeau Farncombe Family Digestive Health Research Institute, Department of Medicine, McMaster University, Hamilton, Ontario, Canada
Marco Constante Farncombe Family Digestive Health Research Institute, Department of Medicine, McMaster University, Hamilton, Ontario, Canada
Alexandra Clarizio Farncombe Family Digestive Health Research Institute, Department of Medicine, McMaster University, Hamilton, Ontario, Canada
Jennifer Jury Farncombe Family Digestive Health Research Institute, Department of Medicine, McMaster University, Hamilton, Ontario, Canada
Natalia M Breyner Farncombe Family Digestive Health Research Institute, Department of Medicine, McMaster University, Hamilton, Ontario, Canada
Alberto Caminero Farncombe Family Digestive Health Research Institute, Department of Medicine, McMaster University, Hamilton, Ontario, Canada
Gaston Rueda Farncombe Family Digestive Health Research Institute, Department of Medicine, McMaster University, Hamilton, Ontario, Canada
Christina L Hayes Farncombe Family Digestive Health Research Institute, Department of Medicine, McMaster University, Hamilton, Ontario, Canada
Justin L McCarville Farncombe Family Digestive Health Research Institute, Department of Medicine, McMaster University, Hamilton, Ontario, Canada
Miriam Bermudez Brito Farncombe Family Digestive Health Research Institute, Department of Medicine, McMaster University, Hamilton, Ontario, Canada
Julien Planchais Université Paris-Saclay, INRAE, AgroParisTech, Micalis Institute, 78350, Jouy-en-Josas, France
Nathalie Rolhion Sorbonne Université, Inserm, Centre de Recherche Saint-Antoine, CRSA, AP-HP, Hôpital Saint Antoine, Service de Gastroenterologie, F-75012 Paris, France
Joseph A Murray Division of Gastroenterology and Hepatology, Department of Immunology, Mayo Clinic College of Medicine, Rochester, MN, USA
Philippe Langella Université Paris-Saclay, INRAE, AgroParisTech, Micalis Institute, 78350, Jouy-en-Josas, France
Linda M P Loonen Host-Microbe Interactomics, Animal Sciences Group, Wageningen University, Wageningen, Netherlands
Jerry M Wells Host-Microbe Interactomics, Animal Sciences Group, Wageningen University, Wageningen, Netherlands
Premysl Bercik Farncombe Family Digestive Health Research Institute, Department of Medicine, McMaster University, Hamilton, Ontario, Canada
Harry Sokol Université Paris-Saclay, INRAE, AgroParisTech, Micalis Institute, 78350, Jouy-en-Josas, France. .,Sorbonne Université, Inserm, Centre de Recherche Saint-Antoine, CRSA, AP-HP, Hôpital Saint Antoine, Service de Gastroenterologie, F-75012 Paris, France
Elena F Verdu Farncombe Family Digestive Health Research Institute, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.

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Voisine J, Abadie V. Interplay Between Gluten, HLA, Innate and Adaptive Immunity Orchestrates the Development of Coeliac Disease. Front Immunol 2021;12:674313. [PMID: 34149709 PMCID: PMC8206552 DOI: 10.3389/fimmu.2021.674313] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Accepted: 05/18/2021] [Indexed: 12/26/2022] Open

Bakker OB, Ramírez-Sánchez AD, Borek ZA, de Klein N, Li Y, Modderman R, Kooy-Winkelaar Y, Johannesen MK, Matarese F, Martens JHA, Kumar V, van Bergen J, Qiao SW, Lundin KEA, Sollid LM, Koning F, Wijmenga C, Withoff S, Jonkers IH. Potential impact of celiac disease genetic risk factors on T cell receptor signaling in gluten-specific CD4+ T cells. Sci Rep 2021;11:9252. [PMID: 33927210 PMCID: PMC8085175 DOI: 10.1038/s41598-021-86612-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2020] [Accepted: 03/18/2021] [Indexed: 02/08/2023] Open

Affiliation(s)

Olivier B Bakker Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
Aarón D Ramírez-Sánchez Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
Zuzanna A Borek Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
Niek de Klein Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
Yang Li Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
Rutger Modderman Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
Yvonne Kooy-Winkelaar Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands
Marie K Johannesen K.G. Jebsen Coeliac Disease Research Centre, Institute of Clinical Medicine, University of Oslo, Oslo, Norway Department of Immunology, Oslo University Hospital, Rikshospitalet, Oslo, Norway
Filomena Matarese Department of Molecular Biology, Nijmegen Centre for Molecular Life Sciences, Radboud University, Nijmegen, The Netherlands
Joost H A Martens Department of Molecular Biology, Nijmegen Centre for Molecular Life Sciences, Radboud University, Nijmegen, The Netherlands
Vinod Kumar Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands Nitte (Deemed to be University), Division of Infectious Diseases, Nitte University Centre for Science Education and Research (NUCSER), Paneer Campus, Deralakatte, Mangaluru, 575018, India
Jeroen van Bergen Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands
Shuo-Wang Qiao K.G. Jebsen Coeliac Disease Research Centre, Institute of Clinical Medicine, University of Oslo, Oslo, Norway Department of Immunology, Oslo University Hospital, Rikshospitalet, Oslo, Norway
Knut E A Lundin K.G. Jebsen Coeliac Disease Research Centre, Institute of Clinical Medicine, University of Oslo, Oslo, Norway Department of Gastroenterology, Oslo University Hospital, Rikshospitalet, Oslo, Norway
Ludvig M Sollid K.G. Jebsen Coeliac Disease Research Centre, Institute of Clinical Medicine, University of Oslo, Oslo, Norway Department of Immunology, Oslo University Hospital, Rikshospitalet, Oslo, Norway
Frits Koning Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands
Cisca Wijmenga Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands K.G. Jebsen Coeliac Disease Research Centre, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
Sebo Withoff Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
Iris H Jonkers Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

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Caproni M, Capone M, Rossi MC, Santarlasci V, Maggi L, Mazzoni A, Rossettini B, Renzi D, Quintarelli L, Bianchi B, Ninci A, Lami G, Calabrò A, Cosmi L, Annunziato F, Liotta F. T Cell Response Toward Tissue-and Epidermal-Transglutaminases in Coeliac Disease Patients Developing Dermatitis Herpetiformis. Front Immunol 2021;12:645143. [PMID: 33959126 PMCID: PMC8093623 DOI: 10.3389/fimmu.2021.645143] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2020] [Accepted: 03/24/2021] [Indexed: 12/19/2022] Open

Affiliation(s)

Marzia Caproni Rare Diseases Unit, Section of Dermatology, Department of Health Sciences, USL Toscana Centro, University of Florence, European Reference Network-Skin Member, Florence, Italy
Manuela Capone Department of Experimental and Clinical Medicine, School of Human Health Sciences, University of Florence, Florence, Italy
Maria Caterina Rossi Department of Experimental and Clinical Medicine, School of Human Health Sciences, University of Florence, Florence, Italy
Veronica Santarlasci Department of Experimental and Clinical Medicine, School of Human Health Sciences, University of Florence, Florence, Italy
Laura Maggi Department of Experimental and Clinical Medicine, School of Human Health Sciences, University of Florence, Florence, Italy
Alessio Mazzoni Department of Experimental and Clinical Medicine, School of Human Health Sciences, University of Florence, Florence, Italy
Beatrice Rossettini Department of Experimental and Clinical Medicine, School of Human Health Sciences, University of Florence, Florence, Italy
Daniela Renzi Department of Biomedical Experimental and Clinical Sciences "Mario Serio", University of Florence, Florence, Italy
Lavinia Quintarelli Rare Diseases Unit, Section of Dermatology, Department of Health Sciences, USL Toscana Centro, University of Florence, European Reference Network-Skin Member, Florence, Italy
Beatrice Bianchi Department of Health Sciences, University of Florence, Florence, Italy
Alessandra Ninci Medical Specialization School of Hygiene and Preventive Medicine, University of Florence, Florence, Italy
Gabriele Lami Department of Biomedical Experimental and Clinical Sciences "Mario Serio", University of Florence, Florence, Italy
Antonio Calabrò Department of Biomedical Experimental and Clinical Sciences "Mario Serio", University of Florence, Florence, Italy
Lorenzo Cosmi Department of Experimental and Clinical Medicine, School of Human Health Sciences, University of Florence, Florence, Italy
Francesco Annunziato Department of Experimental and Clinical Medicine, School of Human Health Sciences, University of Florence, Florence, Italy
Francesco Liotta Department of Experimental and Clinical Medicine, School of Human Health Sciences, University of Florence, Florence, Italy

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van Wanrooij RLJ, Bontkes HJ, Neefjes-Borst EA, Mulder CJ, Bouma G. Immune-mediated enteropathies: From bench to bedside. J Autoimmun 2021;118:102609. [PMID: 33607573 DOI: 10.1016/j.jaut.2021.102609] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2020] [Revised: 01/22/2021] [Accepted: 01/23/2021] [Indexed: 12/13/2022]

Cellular and molecular bases of refractory celiac disease. INTERNATIONAL REVIEW OF CELL AND MOLECULAR BIOLOGY 2021;358:207-240. [PMID: 33707055 DOI: 10.1016/bs.ircmb.2020.12.001] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]

Wyrożemski Ł, Sollid LM, Qiao SW. C-type lectin-like CD161 is not a co-signalling receptor in gluten-reactive CD4 + T cells. Scand J Immunol 2021;93:e13016. [PMID: 33368526 DOI: 10.1111/sji.13016] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2020] [Revised: 12/17/2020] [Accepted: 12/18/2020] [Indexed: 11/28/2022]

Dias R, Pereira CB, Pérez-Gregorio R, Mateus N, Freitas V. Recent advances on dietary polyphenol's potential roles in Celiac Disease. Trends Food Sci Technol 2021. [DOI: 10.1016/j.tifs.2020.10.033] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]

Abadie V. [A new mouse model of coeliac disease with villous atrophy]. Med Sci (Paris) 2020;36:969-972. [PMID: 33151855 DOI: 10.1051/medsci/2020184] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open

Arranz E, De Prado Á, Fiz-López A, Arribas E, Garrote JA, Bernardo D. Human intestinal dendritic cell and macrophage subsets in coeliac disease. INTERNATIONAL REVIEW OF CELL AND MOLECULAR BIOLOGY 2020;358:85-104. [PMID: 33707058 DOI: 10.1016/bs.ircmb.2020.09.006] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]

Dunne MR, Byrne G, Chirdo FG, Feighery C. Coeliac Disease Pathogenesis: The Uncertainties of a Well-Known Immune Mediated Disorder. Front Immunol 2020;11:1374. [PMID: 32733456 PMCID: PMC7360848 DOI: 10.3389/fimmu.2020.01374] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2019] [Accepted: 05/28/2020] [Indexed: 12/21/2022] Open

Picascia S, Camarca A, Malamisura M, Mandile R, Galatola M, Cielo D, Gazza L, Mamone G, Auricchio S, Troncone R, Greco L, Auricchio R, Gianfrani C. In Celiac Disease Patients the In Vivo Challenge with the Diploid Triticum monococcum Elicits a Reduced Immune Response Compared to Hexaploid Wheat. Mol Nutr Food Res 2020;64:e1901032. [PMID: 32374905 DOI: 10.1002/mnfr.201901032] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2019] [Revised: 02/11/2020] [Indexed: 12/27/2022]

Affiliation(s)

Stefania Picascia Institute of Biochemistry and Cell Biology, National Research Council, Via Pietro Castellino, 111, Napoli, Naples, 80131, Italy
Alessandra Camarca Institute of Food Sciences, National Research Council, Via Roma, 64, Avellino, 83100, Italy
Monica Malamisura Department of Medical Translational Sciences, Section of Pediatrics, Federico II University of Naples, Via Sergio Pansini, 5, Napoli, 80131, Italy
Roberta Mandile Department of Medical Translational Sciences, Section of Pediatrics, Federico II University of Naples, Via Sergio Pansini, 5, Napoli, 80131, Italy
Martina Galatola Department of Medical Translational Sciences, Section of Pediatrics, Federico II University of Naples, Via Sergio Pansini, 5, Napoli, 80131, Italy
Donatella Cielo Department of Medical Translational Sciences, Section of Pediatrics, Federico II University of Naples, Via Sergio Pansini, 5, Napoli, 80131, Italy
Laura Gazza CREA Research Centre for Engineering and Agro-Food Processing, Via Po, 14, Roma, 00198, Italy
Gianfranco Mamone Institute of Food Sciences, National Research Council, Via Roma, 64, Avellino, 83100, Italy
Salvatore Auricchio Department of Medical Translational Sciences, Section of Pediatrics, Federico II University of Naples, Via Sergio Pansini, 5, Napoli, 80131, Italy.,European Laboratory for the Food Induced Diseases (E.L.F.I.D), Federico II University of Naples, Via Sergio Pansini, 5, Napoli, 80131, Italy
Riccardo Troncone Department of Medical Translational Sciences, Section of Pediatrics, Federico II University of Naples, Via Sergio Pansini, 5, Napoli, 80131, Italy.,European Laboratory for the Food Induced Diseases (E.L.F.I.D), Federico II University of Naples, Via Sergio Pansini, 5, Napoli, 80131, Italy
Luigi Greco Department of Medical Translational Sciences, Section of Pediatrics, Federico II University of Naples, Via Sergio Pansini, 5, Napoli, 80131, Italy.,European Laboratory for the Food Induced Diseases (E.L.F.I.D), Federico II University of Naples, Via Sergio Pansini, 5, Napoli, 80131, Italy
Renata Auricchio Department of Medical Translational Sciences, Section of Pediatrics, Federico II University of Naples, Via Sergio Pansini, 5, Napoli, 80131, Italy.,European Laboratory for the Food Induced Diseases (E.L.F.I.D), Federico II University of Naples, Via Sergio Pansini, 5, Napoli, 80131, Italy
Carmen Gianfrani Institute of Biochemistry and Cell Biology, National Research Council, Via Pietro Castellino, 111, Napoli, Naples, 80131, Italy.,European Laboratory for the Food Induced Diseases (E.L.F.I.D), Federico II University of Naples, Via Sergio Pansini, 5, Napoli, 80131, Italy

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Iron Absorption in Celiac Disease and Nutraceutical Effect of 7-Hydroxymatairesinol. Mini-Review. Molecules 2020;25:molecules25092041. [PMID: 32349426 PMCID: PMC7249079 DOI: 10.3390/molecules25092041] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2020] [Revised: 04/19/2020] [Accepted: 04/23/2020] [Indexed: 12/23/2022] Open

Abstract

Anemia is the main extra-gastrointestinal symptom in inflammatory bowel diseases (IBDs). Interleukin-6 (IL-6) and other cytokines are secreted and act in the microenvironment of the small intestine mucous membrane of IBD patients. Iron is essential for multiple cell functions and its homeostasis is regulated by the hepcidin–ferroportin axis. Hepcidin (HEPC) is mainly produced by the liver in response to iron needs but is also an acute phase protein. During inflammation, hepcidin is upregulated by IL-6 and is responsible for iron compartmentalization within cells, in turn causing anemia of inflammation. Tissues other than liver can produce hepcidin in response to inflammatory stimuli, in order to decrease iron efflux at a local level, then acting in an autocrine–paracrine manner. In IBDs and, in particular, in celiac disease (CeD), IL-6 might trigger the expression, upregulation and secretion of hepcidin in the small intestine, reducing iron efflux and exacerbating defective iron absorption. 7-Hydroxymatairesinol (7-HMR) belongs to the family of lignans, polyphenolic compounds produced by plants, and has nutraceutical antioxidant, anti-inflammatory and estrogenic properties. In this mini-review we revise the role of inflammation in IBDs and in particular in CeD, focusing our attention on the close link among inflammation, anemia and iron metabolism. We also briefly describe the anti-inflammatory and estrogenic activity of 7-HMR contained in foods that are often consumed by CeD patients. Finally, considering that HEPC expression is regulated by iron needs, inflammation and estrogens, we explored the hypothesis that 7-HMR consumption could ameliorate anemia in CeD using Caco-2 cells as bowel model. Further studies are needed to verify the regulation pathway through which 7-HMR may interfere with the local production of HEPC in bowel.

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Iervasi E, Auricchio R, Strangio A, Greco L, Saverino D. Serum IL-21 levels from celiac disease patients correlates with anti-tTG IgA autoantibodies and mucosal damage. Autoimmunity 2020;53:225-230. [PMID: 32157915 DOI: 10.1080/08916934.2020.1736047] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]

Zorro MM, Aguirre-Gamboa R, Mayassi T, Ciszewski C, Barisani D, Hu S, Weersma RK, Withoff S, Li Y, Wijmenga C, Jabri B, Jonkers IH. Tissue alarmins and adaptive cytokine induce dynamic and distinct transcriptional responses in tissue-resident intraepithelial cytotoxic T lymphocytes. J Autoimmun 2020;108:102422. [PMID: 32033836 PMCID: PMC7049906 DOI: 10.1016/j.jaut.2020.102422] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2019] [Revised: 01/28/2020] [Accepted: 01/28/2020] [Indexed: 12/13/2022]

Affiliation(s)

Maria Magdalena Zorro Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
Raul Aguirre-Gamboa Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
Toufic Mayassi Department of Medicine, University of Chicago, Chicago, USA; Committee on Immunology, University of Chicago, Chicago, USA
Cezary Ciszewski Department of Medicine, University of Chicago, Chicago, USA
Donatella Barisani School of Medicine and Surgery, University of Milano-Bicocca, Italy
Shixian Hu Department of Gastroenterology and Hepatology, University Medical Center, Groningen, University of Groningen, Groningen, the Netherlands
Rinse K Weersma Department of Gastroenterology and Hepatology, University Medical Center, Groningen, University of Groningen, Groningen, the Netherlands
Sebo Withoff Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
Yang Li Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands; Department of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, the Netherlands; Department of Computational Biology for Individualised Infection Medicine, Centre for Individualised Infection Medicine, Helmholtz Centre for Infection Research, Hannover Medical School. Hannover, Germany
Cisca Wijmenga Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands; K.G. Jebsen Coeliac Disease Research Centre, Department of Immunology, University of Oslo, Oslo, Norway
Bana Jabri Department of Medicine, University of Chicago, Chicago, USA; Committee on Immunology, University of Chicago, Chicago, USA.
Iris H Jonkers Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands; K.G. Jebsen Coeliac Disease Research Centre, Department of Immunology, University of Oslo, Oslo, Norway.

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Sharma N, Bhatia S, Chunduri V, Kaur S, Sharma S, Kapoor P, Kumari A, Garg M. Pathogenesis of Celiac Disease and Other Gluten Related Disorders in Wheat and Strategies for Mitigating Them. Front Nutr 2020;7:6. [PMID: 32118025 PMCID: PMC7020197 DOI: 10.3389/fnut.2020.00006] [Citation(s) in RCA: 77] [Impact Index Per Article: 15.4] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2019] [Accepted: 01/20/2020] [Indexed: 12/12/2022] Open

Ciszewski C, Discepolo V, Pacis A, Doerr N, Tastet O, Mayassi T, Maglio M, Basheer A, Al-Mawsawi LQ, Green P, Auricchio R, Troncone R, Waldmann TA, Azimi N, Tagaya Y, Barreiro LB, Jabri B. Identification of a γc Receptor Antagonist That Prevents Reprogramming of Human Tissue-resident Cytotoxic T Cells by IL15 and IL21. Gastroenterology 2020;158:625-637.e13. [PMID: 31622625 PMCID: PMC7861144 DOI: 10.1053/j.gastro.2019.10.006] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2019] [Revised: 10/02/2019] [Accepted: 10/04/2019] [Indexed: 12/23/2022]

Abstract

BACKGROUND & AIMS

Gamma chain (γc) cytokines (interleukin [IL]2, IL4, IL7, IL9, IL15, and IL21) signal via a common γc receptor. IL2 regulates the immune response, whereas IL21 and IL15 contribute to development of autoimmune disorders, including celiac disease. We investigated whether BNZ-2, a peptide designed to inhibit IL15 and IL21, blocks these cytokines selectively and its effects on intraepithelial cytotoxic T cells.

METHODS

We obtained duodenal biopsies from 9 patients with potential celiac disease (positive results from tests for anti-TG2 but no villous atrophy), 30 patients with untreated celiac disease (with villous atrophy), and 5 patients with treated celiac disease (on a gluten-free diet), as well as 43 individuals without celiac disease (controls). We stimulated primary intestinal intraepithelial CD8⁺ T-cell lines, or CD8⁺ T cells directly isolated from intestinal biopsies, with γc cytokines in presence or absence of BNZ-2. Cells were analyzed by immunoblots, flow cytometry, or RNA-sequencing analysis for phosphorylation of signaling molecules, gene expression profiles, proliferation, and levels of granzyme B.

RESULTS

Duodenal tissues from patients with untreated celiac disease had increased levels of messenger RNAs encoding IL15 receptor subunit alpha (IL15RA) and IL21 compared with tissues from patients with potential celiac disease and controls. Activation of intraepithelial cytotoxic T cells with IL15 or IL21 induced separate signaling pathways; incubation of the cells with IL15 and IL21 cooperatively increased their transcriptional activity, proliferation, and cytolytic properties. BNZ-2 specifically inhibited the effects of IL15 and IL21, but not of other γc cytokines.

CONCLUSIONS

We found increased expression of IL15RA and IL21 in duodenal tissues from patients with untreated celiac disease compared with controls. IL15 and IL21 cooperatively activated intestinal intraepithelial cytotoxic T cells. In particular, they increased their transcriptional activity, proliferation, and cytolytic activity. The peptide BNZ-2 blocked these effects, but not those of other γc cytokines, including IL2. BNZ-2 might be used to prevent cytotoxic T-cell-mediated tissue damage in complex immune disorders exhibiting upregulation of IL15 and IL21.

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Affiliation(s)

Cezary Ciszewski Department of Medicine, University of Chicago, Chicago, IL, USA
Valentina Discepolo Department of Medicine, University of Chicago, Chicago, IL, USA
Alain Pacis Department of Genetics, CHU Sainte-Justine Research Center, Montreal, QC, Canada
Nick Doerr Bioniz Therapeutics, Inc., Irvine, CA, USA
Olivier Tastet Department of Genetics, CHU Sainte-Justine Research Center, Montreal, QC, Canada
Toufic Mayassi Department of Medicine, University of Chicago, Chicago, IL, USA.,4Committee on Immunology, University of Chicago, Chicago, IL, USA
Mariantonia Maglio Department of Translational Medical Science and European Laboratory for the Investigation of Food Induced Diseases (ELFID), Università degli Studi di Napoli Federico II, Napoli, Italy
Asjad Basheer Bioniz Therapeutics, Inc., Irvine, CA, USA
Laith Q. Al-Mawsawi Bioniz Therapeutics, Inc., Irvine, CA, USA
Peter Green Celiac Disease Center, Columbia University, New York, NY, USA
Renata Auricchio Department of Translational Medical Science and European Laboratory for the Investigation of Food Induced Diseases (ELFID), Università degli Studi di Napoli Federico II, Napoli, Italy
Riccardo Troncone Department of Translational Medical Science and European Laboratory for the Investigation of Food Induced Diseases (ELFID), Università degli Studi di Napoli Federico II, Napoli, Italy
Thomas A. Waldmann Lymphoid Malignancies Branch, National Cancer Institute, Bethesda, Maryland, USA
Nazli Azimi Bioniz Therapeutics, Inc., Irvine, CA, USA
Yutaka Tagaya Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA
Luis B. Barreiro Department of Medicine, University of Chicago, Chicago, IL, USA.,9Committee on Genetics, Genomics and Systems Biology, University of Chicago, Chicago, IL, USA
Bana Jabri Department of Medicine, University of Chicago, Chicago, Illinois; Committee on Immunology, University of Chicago, Chicago, Illinois; Department of Pathology and Pediatrics, University of Chicago, Chicago, Illinois.

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Abadie V, Kim SM, Lejeune T, Palanski BA, Ernest JD, Tastet O, Voisine J, Discepolo V, Marietta EV, Hawash MBF, Ciszewski C, Bouziat R, Panigrahi K, Horwath I, Zurenski MA, Lawrence I, Dumaine A, Yotova V, Grenier JC, Murray JA, Khosla C, Barreiro LB, Jabri B. IL-15, gluten and HLA-DQ8 drive tissue destruction in coeliac disease. Nature 2020;578:600-604. [PMID: 32051586 PMCID: PMC7047598 DOI: 10.1038/s41586-020-2003-8] [Citation(s) in RCA: 147] [Impact Index Per Article: 29.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2018] [Accepted: 12/16/2019] [Indexed: 11/09/2022]

Affiliation(s)

Valérie Abadie Department of Microbiology, Infectiology, and Immunology, Faculty of Medicine, University of Montreal, Montreal, Quebec, Canada. Sainte-Justine Hospital Research Centre, University of Montreal, Montreal, Quebec, Canada. Department of Medicine, University of Chicago, Chicago, IL, USA.
Sangman M Kim Department of Medicine, University of Chicago, Chicago, IL, USA Committee on Immunology, University of Chicago, Chicago, IL, USA Department of Biology, University of San Francisco, San Francisco, CA, USA
Thomas Lejeune Department of Microbiology, Infectiology, and Immunology, Faculty of Medicine, University of Montreal, Montreal, Quebec, Canada Sainte-Justine Hospital Research Centre, University of Montreal, Montreal, Quebec, Canada
Brad A Palanski Department of Chemistry, Stanford University, Stanford, CA, USA
Jordan D Ernest Department of Medicine, University of Chicago, Chicago, IL, USA Committee on Immunology, University of Chicago, Chicago, IL, USA
Olivier Tastet Department of Genetics, Sainte-Justine Hospital Research Centre, University of Montreal, Montreal, Quebec, Canada
Jordan Voisine Department of Medicine, University of Chicago, Chicago, IL, USA Committee on Immunology, University of Chicago, Chicago, IL, USA
Valentina Discepolo Department of Medicine, University of Chicago, Chicago, IL, USA
Eric V Marietta Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA Department of Immunology, Mayo Clinic, Rochester, MN, USA Department of Dermatology, Mayo Clinic, Rochester, MN, USA
Mohamed B F Hawash Department of Genetics, Sainte-Justine Hospital Research Centre, University of Montreal, Montreal, Quebec, Canada Department of Biochemistry, Faculty of Medicine, University of Montreal, Montreal, Quebec, Canada
Cezary Ciszewski Department of Medicine, University of Chicago, Chicago, IL, USA Committee on Immunology, University of Chicago, Chicago, IL, USA
Romain Bouziat Department of Medicine, University of Chicago, Chicago, IL, USA Committee on Immunology, University of Chicago, Chicago, IL, USA
Kaushik Panigrahi Department of Medicine, University of Chicago, Chicago, IL, USA
Irina Horwath Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
Matthew A Zurenski Department of Medicine, University of Chicago, Chicago, IL, USA
Ian Lawrence Department of Medicine, University of Chicago, Chicago, IL, USA
Anne Dumaine Department of Genetics, Sainte-Justine Hospital Research Centre, University of Montreal, Montreal, Quebec, Canada
Vania Yotova Department of Genetics, Sainte-Justine Hospital Research Centre, University of Montreal, Montreal, Quebec, Canada
Jean-Christophe Grenier Department of Genetics, Sainte-Justine Hospital Research Centre, University of Montreal, Montreal, Quebec, Canada
Joseph A Murray Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
Chaitan Khosla Department of Chemistry, Stanford University, Stanford, CA, USA Department of Chemical Engineering, Stanford University, Stanford, CA, USA Stanford ChEM-H, Stanford University, Stanford, CA, USA
Luis B Barreiro Department of Genetics, Sainte-Justine Hospital Research Centre, University of Montreal, Montreal, Quebec, Canada Department of Pediatrics, Faculty of Medicine, University of Montreal, Montreal, Quebec, Canada Department of Medicine, Section of Genetic Medicine, University of Chicago, Chicago, IL, USA
Bana Jabri Department of Medicine, University of Chicago, Chicago, IL, USA. Committee on Immunology, University of Chicago, Chicago, IL, USA. Department of Pediatrics, Section of Gastroenterology, Hepatology and Nutrition, University of Chicago, Chicago, IL, USA. Department of Pathology, University of Chicago, Chicago, IL, USA. University of Chicago Celiac Disease Center, University of Chicago, Chicago, IL, USA.

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Caio G, Ciccocioppo R, Zoli G, De Giorgio R, Volta U. Therapeutic options for coeliac disease: What else beyond gluten-free diet? Dig Liver Dis 2020;52:130-137. [PMID: 31831308 DOI: 10.1016/j.dld.2019.11.010] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2019] [Revised: 11/12/2019] [Accepted: 11/17/2019] [Indexed: 12/11/2022]

Goel G, Daveson AJM, Hooi CE, Tye-Din JA, Wang S, Szymczak E, Williams LJ, Dzuris JL, Neff KM, Truitt KE, Anderson RP. Serum cytokines elevated during gluten-mediated cytokine release in coeliac disease. Clin Exp Immunol 2019;199:68-78. [PMID: 31505020 DOI: 10.1111/cei.13369] [Citation(s) in RCA: 42] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/02/2019] [Indexed: 12/14/2022] Open

Abstract

Cytokines have been extensively studied in coeliac disease, but cytokine release related to exposure to gluten and associated symptoms has only recently been described. Prominent, early elevations in serum interleukin (IL)-2 after gluten support a central role for T cell activation in the clinical reactions to gluten in coeliac disease. The aim of this study was to establish a quantitative hierarchy of serum cytokines and their relation to symptoms in patients with coeliac disease during gluten-mediated cytokine release reactions. Sera were analyzed from coeliac disease patients on a gluten free-diet (n = 25) and from a parallel cohort of healthy volunteers (n = 25) who underwent an unmasked gluten challenge. Sera were collected at baseline and 2, 4 and 6 h after consuming 10 g vital wheat gluten flour; 187 cytokines were assessed. Confirmatory analyses were performed by high-sensitivity electrochemiluminescence immunoassay. Cytokine elevations were correlated with symptoms. Cytokine release following gluten challenge in coeliac disease patients included significant elevations of IL-2, chemokine (C-C motif) ligand 20 (CCL20), IL-6, chemokine (C-X-C motif) ligand (CXCL)9, CXCL8, interferon (IFN)-γ, IL-10, IL-22, IL-17A, tumour necrosis factor (TNF)-α, CCL2 and amphiregulin. IL-2 and IL-17A were earliest to rise. Peak levels of cytokines were generally at 4 h. IL-2 increased most (median 57-fold), then CCL20 (median 10-fold). Cytokine changes were strongly correlated with one another, and the most severely symptomatic patients had the highest elevations. Early elevations of IL-2, IL-17A, IL-22 and IFN-γ after gluten in patients with coeliac disease implicates rapidly activated T cells as their probable source. Cytokine release after gluten could aid in monitoring experimental treatments and support diagnosis.

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Vitale S, Santarlasci V, Camarca A, Picascia S, Pasquale AD, Maglio M, Maggi E, Cosmi L, Annunziato F, Troncone R, Auricchio R, Gianfrani C. The intestinal expansion of TCRγδ⁺ and disappearance of IL4⁺ T cells suggest their involvement in the evolution from potential to overt celiac disease. Eur J Immunol 2019;49:2222-2234. [PMID: 31553811 DOI: 10.1002/eji.201948098] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2019] [Revised: 07/26/2019] [Indexed: 01/03/2023]

Coeliac Disease and Mast Cells. Int J Mol Sci 2019;20:ijms20143400. [PMID: 31373285 PMCID: PMC6678566 DOI: 10.3390/ijms20143400] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2019] [Revised: 07/05/2019] [Accepted: 07/08/2019] [Indexed: 01/01/2023] Open

Costes LMM, Lindenbergh-Kortleve DJ, van Berkel LA, Veenbergen S, Raatgeep HRC, Simons-Oosterhuis Y, van Haaften DH, Karrich JJ, Escher JC, Groeneweg M, Clausen BE, Cupedo T, Samsom JN. IL-10 signaling prevents gluten-dependent intraepithelial CD4⁺ cytotoxic T lymphocyte infiltration and epithelial damage in the small intestine. Mucosal Immunol 2019;12:479-490. [PMID: 30542112 DOI: 10.1038/s41385-018-0118-0] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2018] [Revised: 10/18/2018] [Accepted: 11/16/2018] [Indexed: 02/04/2023]

Affiliation(s)

L M M Costes Laboratory of Pediatrics, Division of Gastroenterology and Nutrition, Erasmus University Medical Center-Sophia Children's Hospital, Rotterdam, 3000 CA, The Netherlands
D J Lindenbergh-Kortleve Laboratory of Pediatrics, Division of Gastroenterology and Nutrition, Erasmus University Medical Center-Sophia Children's Hospital, Rotterdam, 3000 CA, The Netherlands
L A van Berkel Laboratory of Pediatrics, Division of Gastroenterology and Nutrition, Erasmus University Medical Center-Sophia Children's Hospital, Rotterdam, 3000 CA, The Netherlands
S Veenbergen Laboratory of Pediatrics, Division of Gastroenterology and Nutrition, Erasmus University Medical Center-Sophia Children's Hospital, Rotterdam, 3000 CA, The Netherlands
H R C Raatgeep Laboratory of Pediatrics, Division of Gastroenterology and Nutrition, Erasmus University Medical Center-Sophia Children's Hospital, Rotterdam, 3000 CA, The Netherlands
Y Simons-Oosterhuis Laboratory of Pediatrics, Division of Gastroenterology and Nutrition, Erasmus University Medical Center-Sophia Children's Hospital, Rotterdam, 3000 CA, The Netherlands
D H van Haaften Laboratory of Pediatrics, Division of Gastroenterology and Nutrition, Erasmus University Medical Center-Sophia Children's Hospital, Rotterdam, 3000 CA, The Netherlands
J J Karrich Department of Hematology, Erasmus University Medical Center, Rotterdam, 3000 CA, The Netherlands
J C Escher Department of Pediatric Gastroenterology, Erasmus University Medical Center-Sophia Children's Hospital, Rotterdam, The Netherlands
M Groeneweg Department of Pediatrics, Maasstad Hospital, Rotterdam, 3079 DZ, The Netherlands
B E Clausen Institute for Molecular Medicine, University Medical Center of Johannes Gutenberg University, Mainz, 55131, Germany
T Cupedo Department of Hematology, Erasmus University Medical Center, Rotterdam, 3000 CA, The Netherlands
J N Samsom Laboratory of Pediatrics, Division of Gastroenterology and Nutrition, Erasmus University Medical Center-Sophia Children's Hospital, Rotterdam, 3000 CA, The Netherlands.

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Lindfors K, Ciacci C, Kurppa K, Lundin KEA, Makharia GK, Mearin ML, Murray JA, Verdu EF, Kaukinen K. Coeliac disease. Nat Rev Dis Primers 2019;5:3. [PMID: 30631077 DOI: 10.1038/s41572-018-0054-z] [Citation(s) in RCA: 257] [Impact Index Per Article: 42.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]

Chander U, Leeman-Neill RJ, Bhagat G. Pathogenesis of Enteropathy-Associated T Cell Lymphoma. Curr Hematol Malig Rep 2018;13:308-317. [PMID: 29943210 DOI: 10.1007/s11899-018-0459-5] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]

Cebolla Á, Moreno MDL, Coto L, Sousa C. Gluten Immunogenic Peptides as Standard for the Evaluation of Potential Harmful Prolamin Content in Food and Human Specimen. Nutrients 2018;10:E1927. [PMID: 30563126 PMCID: PMC6316305 DOI: 10.3390/nu10121927] [Citation(s) in RCA: 43] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2018] [Revised: 11/23/2018] [Accepted: 11/29/2018] [Indexed: 12/11/2022] Open

Medrano LM, Pascual V, Bodas A, López-Palacios N, Salazar I, Espino-Paisán L, González-Pérez B, Urcelay E, Mendoza JL, Núñez C. Expression patterns common and unique to ulcerative colitis and celiac disease. Ann Hum Genet 2018;83:86-94. [PMID: 30402962 DOI: 10.1111/ahg.12293] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2018] [Revised: 10/02/2018] [Accepted: 10/15/2018] [Indexed: 12/14/2022]

Tutturen AEV, Dørum S, Clancy T, Reims HM, Christophersen A, Lundin KEA, Sollid LM, de Souza GA, Stamnaes J. Characterization of the Small Intestinal Lesion in Celiac Disease by Label-Free Quantitative Mass Spectrometry. THE AMERICAN JOURNAL OF PATHOLOGY 2018;188:1563-1579. [PMID: 29684362 DOI: 10.1016/j.ajpath.2018.03.017] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/21/2017] [Revised: 02/08/2018] [Accepted: 03/13/2018] [Indexed: 12/16/2022]

Tye-Din JA, Galipeau HJ, Agardh D. Celiac Disease: A Review of Current Concepts in Pathogenesis, Prevention, and Novel Therapies. Front Pediatr 2018;6:350. [PMID: 30519552 PMCID: PMC6258800 DOI: 10.3389/fped.2018.00350] [Citation(s) in RCA: 92] [Impact Index Per Article: 13.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2018] [Accepted: 10/29/2018] [Indexed: 12/14/2022] Open

Jabri B, Sollid LM. T Cells in Celiac Disease. THE JOURNAL OF IMMUNOLOGY 2017;198:3005-3014. [PMID: 28373482 DOI: 10.4049/jimmunol.1601693] [Citation(s) in RCA: 168] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/30/2016] [Accepted: 01/30/2017] [Indexed: 12/30/2022]