Reference Citation Analysis: Find an Article, Find a Category, Find a Journal, Find a Scholar

For: Cheng E, Souza RF, Spechler SJ. Tissue remodeling in eosinophilic esophagitis. Am J Physiol Gastrointest Liver Physiol 2012;303:G1175-87. [PMID: 23019192 PMCID: PMC3532456 DOI: 10.1152/ajpgi.00313.2012] [Citation(s) in RCA: 86] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]

For:	Cheng E, Souza RF, Spechler SJ. Tissue remodeling in eosinophilic esophagitis. Am J Physiol Gastrointest Liver Physiol 2012;303:G1175-87. [PMID: 23019192 PMCID: PMC3532456 DOI: 10.1152/ajpgi.00313.2012] [Citation(s) in RCA: 86] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]

Number

Cited by Other Article(s)

Tanaka T, Tsuruta H, Furukawa K, Akiyoshi H. Computed Tomographic Findings of Eosinophilic Enteritis in Eight Cats: Case Series. Vet Med Sci 2025;11:e70353. [PMID: 40285530 PMCID: PMC12032532 DOI: 10.1002/vms3.70353] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2024] [Revised: 03/27/2025] [Accepted: 04/06/2025] [Indexed: 04/29/2025] Open

Clevenger MH, Wei C, Karami AL, Tsikretsis LE, Carlson DA, Pandolfino JE, Gonsalves N, Winter DR, Whelan KA, Tétreault MP. Esophageal epithelial Ikkβ deletion promotes eosinophilic esophagitis in experimental allergy mouse model. J Allergy Clin Immunol 2025;155:1276-1289. [PMID: 39724973 PMCID: PMC11972898 DOI: 10.1016/j.jaci.2024.12.1070] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2024] [Revised: 11/19/2024] [Accepted: 12/11/2024] [Indexed: 12/28/2024]

Kawami N, Hoshikawa Y, Momma E, Tanabe T, Koeda M, Hoshino S, Iwakiri K. Clinical characteristics of patients with eosinophilic esophagitis and eosinophilic esophageal myositis based on esophageal motility. Esophagus 2025;22:124-130. [PMID: 39438425 DOI: 10.1007/s10388-024-01093-5] [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: 04/02/2024] [Accepted: 10/10/2024] [Indexed: 10/25/2024]

Lim M, Kim T, Kim H, Jang BG, Myung JK, Kim HY. Esophageal ILC2s mediate abnormal epithelial remodeling in eosinophilic esophagitis via Areg-EGFR signaling. Cell Mol Immunol 2025;22:97-110. [PMID: 39653767 PMCID: PMC11685411 DOI: 10.1038/s41423-024-01242-x] [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: 05/17/2024] [Accepted: 11/18/2024] [Indexed: 01/01/2025] Open

Shimonosono M, Morimoto M, Hirose W, Tomita Y, Matsuura N, Flashner S, Ebadi MS, Okayasu EH, Lee CY, Britton WR, Martin C, Wuertz BR, Parikh AS, Sachdeva UM, Ondrey FG, Atigadda VR, Elmets CA, Abrams JA, Muir AB, Klein-Szanto AJ, Weinberg KI, Momen-Heravi F, Nakagawa H. Modeling Epithelial Homeostasis and Perturbation in Three-Dimensional Human Esophageal Organoids. Biomolecules 2024;14:1126. [PMID: 39334892 PMCID: PMC11430971 DOI: 10.3390/biom14091126] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2024] [Revised: 08/01/2024] [Accepted: 08/19/2024] [Indexed: 09/30/2024] Open

Affiliation(s)

Masataka Shimonosono Herbert Irving Comprehensive Cancer Research Center, Columbia University Irving Medical Center, New York, NY 10032, USA; (M.S.); (M.M.); (W.H.); (Y.T.); (N.M.); (S.F.); (M.S.E.); (E.H.O.); (C.Y.L.); (W.R.B.); (C.M.); (A.S.P.); (J.A.A.); (F.M.-H.)
Masaki Morimoto Herbert Irving Comprehensive Cancer Research Center, Columbia University Irving Medical Center, New York, NY 10032, USA; (M.S.); (M.M.); (W.H.); (Y.T.); (N.M.); (S.F.); (M.S.E.); (E.H.O.); (C.Y.L.); (W.R.B.); (C.M.); (A.S.P.); (J.A.A.); (F.M.-H.)
Wataru Hirose Herbert Irving Comprehensive Cancer Research Center, Columbia University Irving Medical Center, New York, NY 10032, USA; (M.S.); (M.M.); (W.H.); (Y.T.); (N.M.); (S.F.); (M.S.E.); (E.H.O.); (C.Y.L.); (W.R.B.); (C.M.); (A.S.P.); (J.A.A.); (F.M.-H.)
Yasuto Tomita Herbert Irving Comprehensive Cancer Research Center, Columbia University Irving Medical Center, New York, NY 10032, USA; (M.S.); (M.M.); (W.H.); (Y.T.); (N.M.); (S.F.); (M.S.E.); (E.H.O.); (C.Y.L.); (W.R.B.); (C.M.); (A.S.P.); (J.A.A.); (F.M.-H.)
Norihiro Matsuura Herbert Irving Comprehensive Cancer Research Center, Columbia University Irving Medical Center, New York, NY 10032, USA; (M.S.); (M.M.); (W.H.); (Y.T.); (N.M.); (S.F.); (M.S.E.); (E.H.O.); (C.Y.L.); (W.R.B.); (C.M.); (A.S.P.); (J.A.A.); (F.M.-H.)
Samuel Flashner Herbert Irving Comprehensive Cancer Research Center, Columbia University Irving Medical Center, New York, NY 10032, USA; (M.S.); (M.M.); (W.H.); (Y.T.); (N.M.); (S.F.); (M.S.E.); (E.H.O.); (C.Y.L.); (W.R.B.); (C.M.); (A.S.P.); (J.A.A.); (F.M.-H.)
Mesra S. Ebadi Herbert Irving Comprehensive Cancer Research Center, Columbia University Irving Medical Center, New York, NY 10032, USA; (M.S.); (M.M.); (W.H.); (Y.T.); (N.M.); (S.F.); (M.S.E.); (E.H.O.); (C.Y.L.); (W.R.B.); (C.M.); (A.S.P.); (J.A.A.); (F.M.-H.)
Emilea H. Okayasu Herbert Irving Comprehensive Cancer Research Center, Columbia University Irving Medical Center, New York, NY 10032, USA; (M.S.); (M.M.); (W.H.); (Y.T.); (N.M.); (S.F.); (M.S.E.); (E.H.O.); (C.Y.L.); (W.R.B.); (C.M.); (A.S.P.); (J.A.A.); (F.M.-H.)
Christian Y. Lee Herbert Irving Comprehensive Cancer Research Center, Columbia University Irving Medical Center, New York, NY 10032, USA; (M.S.); (M.M.); (W.H.); (Y.T.); (N.M.); (S.F.); (M.S.E.); (E.H.O.); (C.Y.L.); (W.R.B.); (C.M.); (A.S.P.); (J.A.A.); (F.M.-H.)
William R. Britton Herbert Irving Comprehensive Cancer Research Center, Columbia University Irving Medical Center, New York, NY 10032, USA; (M.S.); (M.M.); (W.H.); (Y.T.); (N.M.); (S.F.); (M.S.E.); (E.H.O.); (C.Y.L.); (W.R.B.); (C.M.); (A.S.P.); (J.A.A.); (F.M.-H.)
Cecilia Martin Herbert Irving Comprehensive Cancer Research Center, Columbia University Irving Medical Center, New York, NY 10032, USA; (M.S.); (M.M.); (W.H.); (Y.T.); (N.M.); (S.F.); (M.S.E.); (E.H.O.); (C.Y.L.); (W.R.B.); (C.M.); (A.S.P.); (J.A.A.); (F.M.-H.) Organoid & Cell Culture Core, Columbia University Digestive and Liver Diseases Research Center, New York, NY 10032, USA
Beverly R. Wuertz Department of Otolaryngology, Head and Neck Surgery, Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA; (B.R.W.); (F.G.O.)
Anuraag S. Parikh Herbert Irving Comprehensive Cancer Research Center, Columbia University Irving Medical Center, New York, NY 10032, USA; (M.S.); (M.M.); (W.H.); (Y.T.); (N.M.); (S.F.); (M.S.E.); (E.H.O.); (C.Y.L.); (W.R.B.); (C.M.); (A.S.P.); (J.A.A.); (F.M.-H.) Department of Otolaryngology, Head and Neck Surgery, Columbia University, New York, NY 10032, USA
Uma M. Sachdeva Division of Thoracic Surgery, Massachusetts General Hospital, Boston, MA 02114, USA;
Frank G. Ondrey Department of Otolaryngology, Head and Neck Surgery, Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA; (B.R.W.); (F.G.O.)
Venkatram R. Atigadda Department of Dermatology, University of Alabama, Birmingham, AL 35294, USA; (V.R.A.); (C.A.E.)
Craig A. Elmets Department of Dermatology, University of Alabama, Birmingham, AL 35294, USA; (V.R.A.); (C.A.E.)
Julian A. Abrams Herbert Irving Comprehensive Cancer Research Center, Columbia University Irving Medical Center, New York, NY 10032, USA; (M.S.); (M.M.); (W.H.); (Y.T.); (N.M.); (S.F.); (M.S.E.); (E.H.O.); (C.Y.L.); (W.R.B.); (C.M.); (A.S.P.); (J.A.A.); (F.M.-H.) Division of Digestive and Liver Diseases, Department of Medicine, Columbia University Irving Medical Center, New York, NY 10032, USA
Amanda B. Muir Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Children’s Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA;
Andres J. Klein-Szanto Histopathology Facility, Fox Chase Cancer Center, Philadelphia, PA 19111, USA;
Kenneth I. Weinberg Department of Pediatrics, Maternal & Child Health Research Institute, Stanford Cancer Institute, Stanford University, Stanford, CA 94305, USA;
Fatemeh Momen-Heravi Herbert Irving Comprehensive Cancer Research Center, Columbia University Irving Medical Center, New York, NY 10032, USA; (M.S.); (M.M.); (W.H.); (Y.T.); (N.M.); (S.F.); (M.S.E.); (E.H.O.); (C.Y.L.); (W.R.B.); (C.M.); (A.S.P.); (J.A.A.); (F.M.-H.) Cancer Biology and Immunology Laboratory, College of Dental Medicine, Columbia University Irving Medical Center, New York, NY 10032, USA
Hiroshi Nakagawa Herbert Irving Comprehensive Cancer Research Center, Columbia University Irving Medical Center, New York, NY 10032, USA; (M.S.); (M.M.); (W.H.); (Y.T.); (N.M.); (S.F.); (M.S.E.); (E.H.O.); (C.Y.L.); (W.R.B.); (C.M.); (A.S.P.); (J.A.A.); (F.M.-H.) Organoid & Cell Culture Core, Columbia University Digestive and Liver Diseases Research Center, New York, NY 10032, USA Division of Digestive and Liver Diseases, Department of Medicine, Columbia University Irving Medical Center, New York, NY 10032, USA

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Kaneko T, Iwamura C, Kiuchi M, Kurosugi A, Onoue M, Matsumura T, Chiba T, Nakayama T, Kato N, Hirahara K. Amphiregulin-producing T_H2 cells facilitate esophageal fibrosis of eosinophilic esophagitis. THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY. GLOBAL 2024;3:100287. [PMID: 39040657 PMCID: PMC11260569 DOI: 10.1016/j.jacig.2024.100287] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/29/2023] [Revised: 01/26/2024] [Accepted: 03/05/2024] [Indexed: 07/24/2024]

Shaker A. Esophageal remodeling in eosinophilic esophagitis. Curr Opin Gastroenterol 2024;40:291-298. [PMID: 38661722 PMCID: PMC11156539 DOI: 10.1097/mog.0000000000001031] [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] [Indexed: 04/26/2024]

Li T, Salomon M, Shao L, Khalatbari A, Castle JD, Shaker A. Differential Contributions of Fibroblast Subpopulations to Intercellular Communication in Eosinophilic Esophagitis. BIOLOGY 2024;13:461. [PMID: 39056656 PMCID: PMC11273487 DOI: 10.3390/biology13070461] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/12/2024] [Revised: 06/08/2024] [Accepted: 06/17/2024] [Indexed: 07/28/2024]

Low EE, Dellon ES. Review article: Emerging insights into the epidemiology, pathophysiology, diagnostic and therapeutic aspects of eosinophilic oesophagitis and other eosinophilic gastrointestinal diseases. Aliment Pharmacol Ther 2024;59:322-340. [PMID: 38135920 PMCID: PMC10843587 DOI: 10.1111/apt.17845] [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: 07/21/2023] [Revised: 09/08/2023] [Accepted: 12/13/2023] [Indexed: 12/24/2023]

Abstract

BACKGROUND

Eosinophilic gastrointestinal diseases (EGIDs) are chronic, immune-mediated disorders characterised clinically by gastrointestinal symptoms and histologically by a pathologic increase in eosinophil-predominant inflammation in the gastrointestinal tract, in the absence of secondary causes of eosinophilia.

AIMS

To highlight emerging insights and research efforts into the epidemiology, pathophysiology, diagnostic and therapeutic aspects of eosinophilic oesophagitis (EoE) and non-EoE EGIDs, and discuss key remaining knowledge gaps.

METHODS

We selected and reviewed original research, retrospective studies, case series, randomised controlled trials, and meta-analyses.

RESULTS

Standardised nomenclature classifies EGIDs as EoE, eosinophilic gastritis (EoG), eosinophilic enteritis (EoN), and eosinophilic colitis (EoC). Incidence and prevalence of EoE are rising, emphasising the need to better understand how environmental risk factors and genetic features interact. Advances in understanding EoE pathophysiology have led to clinical trials of targeted therapy and the approval (in the United States) of dupilumab for EoE. Several therapies that are under investigation hope to satisfy both histologic and clinical targets. For non-EoE EGIDs, efforts are focused on better defining clinical and histopathologic disease determinants and natural history, as well as establishing new therapies.

CONCLUSIONS

Unmet needs for research are dramatically different for EoE and non-EoE EGIDs. In EoE, non-invasive diagnostic tests, clinicopathologic models that determine the risk of disease progression and therapeutic failure, and novel biologic therapies are emerging. In contrast, in non-EoE EGIDs, epidemiologic trends, diagnostic histopathologic thresholds, and natural history models are still developing for these more rare disorders.

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Thulin H, Säfholm J, Lundahl J, Jovic V, Adner M, Nilsson C. Granzyme B is elevated in esophageal biopsies from children with eosinophilic esophagitis. J Pediatr Gastroenterol Nutr 2024;78:313-319. [PMID: 38374566 DOI: 10.1002/jpn3.12084] [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: 08/24/2023] [Revised: 11/23/2023] [Accepted: 11/28/2023] [Indexed: 02/21/2024]

Arias-González L, Rodríguez-Alcolado L, Laserna-Mendieta EJ, Navarro P, Lucendo AJ, Grueso-Navarro E. Fibrous Remodeling in Eosinophilic Esophagitis: Clinical Facts and Pathophysiological Uncertainties. Int J Mol Sci 2024;25:927. [PMID: 38256003 PMCID: PMC10815180 DOI: 10.3390/ijms25020927] [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: 12/17/2023] [Revised: 01/08/2024] [Accepted: 01/09/2024] [Indexed: 01/24/2024] Open

Affiliation(s)

Laura Arias-González Department of Gastroenterology, Hospital General de Tomelloso, Vereda de Socuéllamos s/n, 13700 Tomelloso, Spain; (L.A.-G.); (L.R.-A.); (E.J.L.-M.); (P.N.); (E.G.-N.) Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 28029 Madrid, Spain Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM), 45071 Toledo, Spain Instituto de Investigación Sanitaria Princesa, 28006 Madrid, Spain
Leticia Rodríguez-Alcolado Department of Gastroenterology, Hospital General de Tomelloso, Vereda de Socuéllamos s/n, 13700 Tomelloso, Spain; (L.A.-G.); (L.R.-A.); (E.J.L.-M.); (P.N.); (E.G.-N.) Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM), 45071 Toledo, Spain
Emilio J. Laserna-Mendieta Department of Gastroenterology, Hospital General de Tomelloso, Vereda de Socuéllamos s/n, 13700 Tomelloso, Spain; (L.A.-G.); (L.R.-A.); (E.J.L.-M.); (P.N.); (E.G.-N.) Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 28029 Madrid, Spain Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM), 45071 Toledo, Spain Instituto de Investigación Sanitaria Princesa, 28006 Madrid, Spain
Pilar Navarro Department of Gastroenterology, Hospital General de Tomelloso, Vereda de Socuéllamos s/n, 13700 Tomelloso, Spain; (L.A.-G.); (L.R.-A.); (E.J.L.-M.); (P.N.); (E.G.-N.) Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 28029 Madrid, Spain Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM), 45071 Toledo, Spain
Alfredo J. Lucendo Department of Gastroenterology, Hospital General de Tomelloso, Vereda de Socuéllamos s/n, 13700 Tomelloso, Spain; (L.A.-G.); (L.R.-A.); (E.J.L.-M.); (P.N.); (E.G.-N.) Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 28029 Madrid, Spain Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM), 45071 Toledo, Spain Instituto de Investigación Sanitaria Princesa, 28006 Madrid, Spain
Elena Grueso-Navarro Department of Gastroenterology, Hospital General de Tomelloso, Vereda de Socuéllamos s/n, 13700 Tomelloso, Spain; (L.A.-G.); (L.R.-A.); (E.J.L.-M.); (P.N.); (E.G.-N.) Instituto de Investigación Sanitaria de Castilla-La Mancha (IDISCAM), 45071 Toledo, Spain

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Rabinowitz SS, Weedon J, Grossman E, Schwarz SM, Nagarajan S, Gress F. Endoscopic Ultrasound Can Measure Esophageal Remodeling in Eosinophilic Esophagitis. TECHNIQUES AND INNOVATIONS IN GASTROINTESTINAL ENDOSCOPY 2024;26:121-129. [DOI: 10.1016/j.tige.2023.12.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/11/2025]

Maslenkina KS, Motylev EN, Guschin MY, Vandysheva RA, Mikhaleva LM. [Pathomorphological criteria and features of immune response in eosinophilic esophagitis and reflux esophagitis]. Arkh Patol 2024;86:5-12. [PMID: 38319266 DOI: 10.17116/patol2024860115] [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] [Indexed: 02/07/2024]

Marella S, Sharma A, Ganesan V, Ferrer-Torres D, Krempski JW, Idelman G, Clark S, Nasiri Z, Vanoni S, Zeng C, Dlugosz AA, Zhou H, Wang S, Doyle AD, Wright BL, Spence JR, Chehade M, Hogan SP. IL-13-induced STAT3-dependent signaling networks regulate esophageal epithelial proliferation in eosinophilic esophagitis. J Allergy Clin Immunol 2023;152:1550-1568. [PMID: 37652141 PMCID: PMC11102758 DOI: 10.1016/j.jaci.2023.07.021] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2023] [Revised: 07/11/2023] [Accepted: 07/21/2023] [Indexed: 09/02/2023]

Abstract

BACKGROUND

Basal zone hyperplasia (BZH) and dilated intercellular spaces (DISs) are thought to contribute to the clinical manifestations of eosinophilic esophagitis (EoE); however, the molecular pathways that drive BZH remain largely unexplored.

OBJECTIVE

We sought to define the role of IL-13-induced transcriptional programs in esophageal epithelial proliferation in EoE.

METHODS

We performed RNA sequencing, bioinformatics, Western blot, reverse transcriptase quantitative PCR, and histologic analyses on esophageal biopsies from healthy control and patients with EoE, primary esophageal cells derived from patients with EoE, and IL-13-stimulated esophageal epithelial keratinocytes grown at the air-liquid interface (EPC2-ALI). Genetic (shRNA) and pharmacologic (proteolysis-targeting chimera degrader) approaches and in vivo model of IL-13-induced esophageal epithelial remodeling (Krt5-rtTA x tetO-IL-13Tg) were used to define the role of signal transducer and activator of transcription 3 (STAT3) and STAT6 and secreted frizzled-related protein 1 (SFRP1) in esophageal epithelial proliferation.

RESULTS

RNA-sequencing analysis of esophageal biopsies (healthy control vs EoE) and EPC2-ALI revealed 82 common differentially expressed genes that were enriched for putative STAT3 target genes. In vitro and in vivo analyses revealed a link between IL-13-induced STAT3 and STAT6 phosphorylation, SFRP1 mRNA expression, and esophageal epithelial proliferation. In vitro studies showed that IL-13-induced esophageal epithelial proliferation was STAT3-dependent and regulated by the STAT3 target SFRP1. SFRP1 mRNA is increased in esophageal biopsies from patients with active EoE compared with healthy controls or patients in remission and identifies an esophageal suprabasal epithelial cell subpopulation that uniquely expressed the core EoE proinflammatory transcriptome genes (CCL26, ALOX15, CAPN14, ANO1, and TNFAIP6).

CONCLUSIONS

These studies identify SFRP1 as a key regulator of IL-13-induced and STAT3-dependent esophageal proliferation and BZH in EoE and link SFRP1+ esophageal epithelial cells with the proinflammatory and epithelial remodeling response in EoE.

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Affiliation(s)

Sahiti Marella Department of Pathology, University of Michigan, Ann Arbor, Mich
Ankit Sharma Department of Pathology, University of Michigan, Ann Arbor, Mich; Mary H. Weiser Food Allergy Center, University of Michigan, Ann Arbor, Mich
Varsha Ganesan Department of Pathology, University of Michigan, Ann Arbor, Mich; Mary H. Weiser Food Allergy Center, University of Michigan, Ann Arbor, Mich
Daysha Ferrer-Torres Internal Medicine, University of Michigan, Ann Arbor, Mich
James W Krempski Department of Pathology, University of Michigan, Ann Arbor, Mich; Mary H. Weiser Food Allergy Center, University of Michigan, Ann Arbor, Mich
Gila Idelman Department of Pathology, University of Michigan, Ann Arbor, Mich; Mary H. Weiser Food Allergy Center, University of Michigan, Ann Arbor, Mich
Sydney Clark Department of Pathology, University of Michigan, Ann Arbor, Mich
Zena Nasiri College of Literature, Science, and the Arts, University of Michigan, Ann Arbor, Mich
Simone Vanoni Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
Chang Zeng Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
Andrej A Dlugosz Department of Dermatology, University of Michigan, Ann Arbor, Mich
Haibin Zhou Pharmacology and Medicinal Chemistry, University of Michigan, Ann Arbor, Mich
Shaomeng Wang Pharmacology and Medicinal Chemistry, University of Michigan, Ann Arbor, Mich
Alfred D Doyle Division of Allergy, Asthma and Immunology, Department of Medicine, Mayo Clinic Arizona, Scottsdale, Ariz
Benjamin L Wright Division of Allergy, Asthma and Immunology, Department of Medicine, Mayo Clinic Arizona, Scottsdale, Ariz; Section of Allergy and Immunology, Division of Pulmonology, Phoenix Children's Hospital, Phoenix, Ariz
Jason R Spence Internal Medicine, University of Michigan, Ann Arbor, Mich
Mirna Chehade Mount Sinai Center for Eosinophilic Disorders, Jaffe Food Allergy Institute, Icahn School of Medicine at Mount Sinai, New York, NY
Simon P Hogan Department of Pathology, University of Michigan, Ann Arbor, Mich; Mary H. Weiser Food Allergy Center, University of Michigan, Ann Arbor, Mich.

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Massironi S, Mulinacci G, Gallo C, Elvevi A, Danese S, Invernizzi P, Vespa E. Mechanistic Insights into Eosinophilic Esophagitis: Therapies Targeting Pathophysiological Mechanisms. Cells 2023;12:2473. [PMID: 37887317 PMCID: PMC10605530 DOI: 10.3390/cells12202473] [Citation(s) in RCA: 22] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2023] [Revised: 10/12/2023] [Accepted: 10/16/2023] [Indexed: 10/28/2023] Open

White E, Mutalib M. Use of endolumenal functional lumen imaging probe in investigating paediatric gastrointestinal motility disorders. World J Clin Pediatr 2023;12:162-170. [PMID: 37753495 PMCID: PMC10518749 DOI: 10.5409/wjcp.v12.i4.162] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2023] [Revised: 08/09/2023] [Accepted: 08/23/2023] [Indexed: 09/06/2023] Open

Klochkova A, Fuller AD, Miller R, Karami AL, Panchani SR, Natarajan S, Mu A, Jackson JL, Klein-Szanto AJ, Muir AB, Whelan KA. A role for age-associated alterations in esophageal epithelium in eosinophilic esophagitis-associated fibrosis. FRONTIERS IN ALLERGY 2022;3:983412. [PMID: 36591561 PMCID: PMC9798296 DOI: 10.3389/falgy.2022.983412] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2022] [Accepted: 11/11/2022] [Indexed: 12/23/2022] Open

de Rooij WE, Diks MAP, Warners MJ, Ampting MTJV, van Esch BCAM, Bredenoord AJ. Gene expression and clinical outcomes after dietary treatment for eosinophilic esophagitis: a prospective study. Neurogastroenterol Motil 2022;34:e14367. [PMID: 35661487 PMCID: PMC9787026 DOI: 10.1111/nmo.14367] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2022] [Revised: 03/12/2022] [Accepted: 03/17/2022] [Indexed: 12/30/2022]

Abstract

BACKGROUND

Eosinophilic esophagitis (EoE) is an allergen-mediated disease and elimination diets have proven to be effective to obtain clinical and histological remission. However, the effect of elimination diets on specific EoE transcripts and their clinical correlates is relatively unknown. The main aim of the study was to evaluate the effect of dietary treatment (four-food elimination diet [FFED]) with or without addition of amino acid-based formula (AAF) on a variety of pro-/anti-inflammatory, epithelial/barrier function and remodeling/fibrosis-related markers of disease activity and clinical correlates (eosinophils, symptoms, and endoscopic signs) in adult EoE patients.

METHODS

We conducted an analysis of biopsy samples and data collected during a randomized controlled trial with an elimination diet in adult patients with active EoE (≥15 eosinophils [eos] per high-power field [hpf]). Demographics, symptoms (SDI-score), endoscopic signs (EREFS) and peak eosinophil counts/hpf were recorded at baseline and after 6 weeks of treatment. Transcripts of 10 indicated genes were measured (qPCR) and compared to clinical correlates at baseline and after treatment.

KEY RESULTS

Forty patients (pooled FFED + FFED + AAF) (60% male, age 34.5 (interquartile range [IQR] 29-42.8 years) completed the diet. Peak eosinophil counts/hpf, symptoms and endoscopic signs were significantly decreased after 6 weeks dietary treatment. DSG-1 levels were significantly upregulated from baseline to week 6, whereas IL-13, CAPN-14, IL-5, IL-10, CCL-26, POSTN, TSLP, CPA-3, and TGF-β were significantly downregulated after 6 weeks of diet (all; <0.01). Prior to treatment, upregulation of CAPN-14 and lower levels of DSG-1 were associated with clinical fibrotic phenotypes, whereas upregulation of IL-10 was linked to food impaction phenotypes.

CONCLUSION

These findings strongly suggest that elimination diets, besides a clinical and histological response, are associated with a broad transcriptional response at the level of the esophageal epithelium.

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Dhar A, Haboubi HN, Attwood SE, Auth MKH, Dunn JM, Sweis R, Morris D, Epstein J, Novelli MR, Hunter H, Cordell A, Hall S, Hayat JO, Kapur K, Moore AR, Read C, Sami SS, Turner PJ, Trudgill NJ. British Society of Gastroenterology (BSG) and British Society of Paediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN) joint consensus guidelines on the diagnosis and management of eosinophilic oesophagitis in children and adults. Gut 2022;71:1459-1487. [PMID: 35606089 PMCID: PMC9279848 DOI: 10.1136/gutjnl-2022-327326] [Citation(s) in RCA: 51] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2022] [Accepted: 05/12/2022] [Indexed: 12/14/2022]

Affiliation(s)

Anjan Dhar Gastroenterology, Darlington Memorial Hospital, Darlington, UK .,Teesside University, Middlesbrough, UK
Hasan N Haboubi Cancer Biomarker Group, Swansea University, Swansea, UK,Department of Gastroenterology, University Hospital Llandough, Llandough, UK
Stephen E Attwood Health Services Research, Durham University, Morpeth, Durham, UK
Marcus K H Auth Department of Paediatric Gastroenterology, Alder Hey Children's NHS Foundation Trust, Liverpool, UK,University of Liverpool, Liverpool, UK
Jason M Dunn Gastroenterology, Guy's and St Thomas' NHS Foundation Trust, London, UK,Comprehensive Cancer Centre, King's College London, London, UK
Rami Sweis Research Department of Tissue and Energy, Division of Surgery & Interventional Science, University College London, London, UK
Danielle Morris Department of Gastroenterology, East and North Hertfordshire NHS Trust, Stevenage, UK
Jenny Epstein Department of Paediatric Gastroenterology, Chelsea and Westminster Hospital NHS Foundation Trust, London, UK
Marco R Novelli Histopathology, University College London, London, UK
Hannah Hunter Department of Dietetics, Guy's and St Thomas' NHS Foundation Trust, London, UK
Amanda Cordell Trustee & Chair, EOS Network, Eosinophilic Disease Charity, London, UK
Sharon Hall Department of Paediatric Allergy, Imperial College Healthcare NHS Trust, London, UK
Jamal O Hayat Gastroenterology, St George's Healthcare NHS Trust, London, UK
Kapil Kapur Gastroenterology, Barnsley Hospital NHS Foundation Trust, Barnsley, UK
Andrew Robert Moore Gastroenterology, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
Carol Read Medical advisor/Patient advocate, EOS Network, Eosinophilic Disease Charity, London, UK
Sarmed S Sami Gastroenterology, University College London Hospitals NHS Foundation Trust, London, UK
Paul J Turner National Heart and Lung Institute Section of Allergy and Clinical Immunology, London, UK,Paediatric Allergy, Imperial College Healthcare NHS Trust, London, UK
Nigel J Trudgill Department of Gastroenterology, Sandwell General Hospital, West Bromwich, UK

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de Souza TA, Carneiro AP, Narciso AS, Barros CP, Alves DA, Marson LB, Tunala T, de Alcântara TM, de Paiva Maia YC, Briza P, Ferreira F, Goulart LR. Eosinophilic esophagitis auxiliary diagnosis based on a peptide ligand to eosinophil cationic protein in esophageal mucus of pediatric patients. Sci Rep 2022;12:12226. [PMID: 35851408 PMCID: PMC9289663 DOI: 10.1038/s41598-022-16293-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2021] [Accepted: 07/07/2022] [Indexed: 11/09/2022] Open

Abstract

Eosinophilic esophagitis (EoE) is a chronic inflammatory condition of the esophagus characterized by increased number of eosinophils. Currently, EoE diagnosis is based on endoscopic procedures for histopathological examination, eosinophils' counting and, often, in clinical practice, the challenge is the differentiation between EoE and gastroesophageal reflux disease (GERD). Our aim was to develop novel peptide ligand to Eosinophil cationic protein (ECP) present in EoE biopsies of patients with potential to be used for detection. We performed a comparative proteomic analysis using liquid chromatography-tandem mass spectrometry (LC-MS/MS) of esophageal biopsies from pediatric patients with eosinophilic esophagitis, gastroesophageal reflux disease and control individuals. Then, phage display technology was used to select peptides against specific up-regulated protein from EoE patients. Twelve phage clones were selected after three biopanning rounds, and the best phage clone reactivity was evaluated by phage-ELISA assay using esophageal mucus samples from 94 pediatric patients. Mass spectrometry showed that eosinophil cationic protein (ECP) was one of the most up-regulated proteins in EoE patients, which is an eosinophil granule protein usually deposited on tissues to mediate remodeling, but in excess may cause fibrosis and hypertrophy, especially in allergic responses. A highly reactive ECP-ligand peptide (E5) was able to distinguish reactive mucus of EoE patients from GERD and the control individuals by Phage-ELISA, achieving a sensitivity of 84.62%, and a specificity of 82.72%. This is the first study that successfully demonstrated an antibody-like peptide targeting ECP at the esophagus mucus as a useful auxilliary tool for EoE diagnosis with a significant association with atopic disorders and dysphagia.ClinicalTrials.gov no.: NCT03069573.

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Tamarit-Sebastian S, Ferrer-Soler FM, Lucendo AJ. Current options and investigational drugs for the treatment of eosinophilic esophagitis. Expert Opin Investig Drugs 2022;31:193-210. [DOI: 10.1080/13543784.2022.2033207] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]

Racca F, Pellegatta G, Cataldo G, Vespa E, Carlani E, Pelaia C, Paoletti G, Messina MR, Nappi E, Canonica GW, Repici A, Heffler E. Type 2 Inflammation in Eosinophilic Esophagitis: From Pathophysiology to Therapeutic Targets. Front Physiol 2022;12:815842. [PMID: 35095572 PMCID: PMC8790151 DOI: 10.3389/fphys.2021.815842] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2021] [Accepted: 12/09/2021] [Indexed: 12/11/2022] Open

Affiliation(s)

Francesca Racca Personalized Medicine, Asthma and Allergy, IRCCS Humanitas Research Hospital, Rozzano, Italy Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy *Correspondence: Francesca Racca,
Gaia Pellegatta Digestive Endoscopy Unit, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Rozzano, Italy
Giuseppe Cataldo Personalized Medicine, Asthma and Allergy, IRCCS Humanitas Research Hospital, Rozzano, Italy
Edoardo Vespa Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy Digestive Endoscopy Unit, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Rozzano, Italy
Elisa Carlani Digestive Endoscopy Unit, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Rozzano, Italy
Corrado Pelaia Department of Medical and Surgical Sciences, University “Magna Graecia” of Catanzaro, Catanzaro, Italy
Giovanni Paoletti Personalized Medicine, Asthma and Allergy, IRCCS Humanitas Research Hospital, Rozzano, Italy Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy
Maria Rita Messina Personalized Medicine, Asthma and Allergy, IRCCS Humanitas Research Hospital, Rozzano, Italy Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy
Emanuele Nappi Personalized Medicine, Asthma and Allergy, IRCCS Humanitas Research Hospital, Rozzano, Italy Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy
Giorgio Walter Canonica Personalized Medicine, Asthma and Allergy, IRCCS Humanitas Research Hospital, Rozzano, Italy Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy
Alessandro Repici Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy Digestive Endoscopy Unit, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Rozzano, Italy
Enrico Heffler Personalized Medicine, Asthma and Allergy, IRCCS Humanitas Research Hospital, Rozzano, Italy Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy

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Azharuddin M, Kapur P, Mishra R, Saleem S, Gupta AK, Adil M, Sharma M. Predictor for cardiovascular risk in patients with type-2 diabetes mellitus. CLINICAL EPIDEMIOLOGY AND GLOBAL HEALTH 2021. [DOI: 10.1016/j.cegh.2021.100870] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open

Medina AL, Troendle DM, Park JY, Thaker A, Dunbar KB, Cheng E. Eosinophilic esophagitis, Barrett's esophagus and esophageal neoplasms in the pediatric patient: a narrative review. Transl Gastroenterol Hepatol 2021;6:32. [PMID: 34423153 DOI: 10.21037/tgh-20-223] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2020] [Accepted: 07/31/2020] [Indexed: 01/07/2023] Open

Lee CH, Choe SJ, Kim DH, Kim EJ, Eom M, Hong SP, Choi EH. Skin atrophy caused by topical glucocorticoids is less common in patients with atopic dermatitis than in those with psoriasis. Exp Dermatol 2021;31:182-190. [PMID: 34351656 DOI: 10.1111/exd.14441] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2020] [Revised: 06/22/2021] [Accepted: 08/02/2021] [Indexed: 11/30/2022]

Antifibrotic Effects of the Thiazolidinediones in Eosinophilic Esophagitis Pathologic Remodeling: A Preclinical Evaluation. Clin Transl Gastroenterol 2021;11:e00164. [PMID: 32352681 PMCID: PMC7263661 DOI: 10.14309/ctg.0000000000000164] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open

Achem SR, Vazquez-Elizondo G, Fass R. Jackhammer Esophagus: Current Concepts and Dilemmas. J Clin Gastroenterol 2021;55:369-379. [PMID: 33337637 DOI: 10.1097/mcg.0000000000001472] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2020] [Accepted: 10/23/2020] [Indexed: 12/27/2022]

Kandikattu HK, Venkateshaiah SU, Verma AK, Mishra A. Tacrolimus (FK506) treatment protects allergen-, IL-5- and IL-13-induced mucosal eosinophilia. Immunology 2021;163:220-235. [PMID: 33512727 DOI: 10.1111/imm.13314] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2020] [Revised: 12/16/2020] [Accepted: 01/18/2021] [Indexed: 02/06/2023] Open

Abstract

Eosinophils are a common clinical feature associated with chronic allergic diseases, and elemental diets, systemic steroids, anti-IL-5 and anti-IL-13 treatment have shown some therapeutic promise. Herein, we present evidence that pre- and post-intraperitoneal administration of tacrolimus (FK506) is very effective in reducing CCR3/Siglec-F⁺ eosinophils in Aspergillus-challenged asthma and EoE, CD2-IL-5 induced global eosinophilia, and DOX regulated IL-13-induced asthma. We used flow cytometry and anti-major basic protein (MBP) immunostaining to examine eosinophils in the spleen, bone marrow, BALF, lung, oesophagus and intestine. Additionally, we also performed ELISA and Western blot analyses to show that tacrolimus treatment also reduces the levels of eosinophil-specific cytokines IL-4, IL-5, IL-13 and TGF-β, eosinophil-specific chemokines Eotaxin-1 and Eotaxin-2, and progenitors of target RCAN1 mRNA and protein levels. Additionally, the current investigations also show that the TGF-β-mediated oesophageal and lung fibrosis is also reduced in Aspergillus-challenged, CD2-IL-5 transgenic and DOX-responsive IL-13 mice. Mechanistically, we show that tacrolimus in vitro treatment inhibited bone marrow-derived eosinophil proliferation and viability by promoting eosinophil apoptosis that may be associated with downregulation of RCAN1. Taken together, we provide in vivo and in vitro evidence that tacrolimus ameliorates eosinophil levels and associated pathogenesis in allergen-, IL-5- and IL-13-induced EoE, EG and asthma pathogenesis. Considering tacrolimus side-effects and reactivity to several other drugs, we propose the topical use of tacrolimus for paediatric and low-dose oral for adult patients as a novel therapeutic strategy for the clinical trial to reduce mucosal eosinophilia first in steroid-refractory or elemental diet non-responsive adult EoE, EG and asthma patients.

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Masterson JC, Menard-Katcher C, Larsen LD, Furuta GT, Spencer LA. Heterogeneity of Intestinal Tissue Eosinophils: Potential Considerations for Next-Generation Eosinophil-Targeting Strategies. Cells 2021;10:cells10020426. [PMID: 33671475 PMCID: PMC7922004 DOI: 10.3390/cells10020426] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2021] [Revised: 02/08/2021] [Accepted: 02/10/2021] [Indexed: 02/05/2023] Open

Affiliation(s)

Joanne C. Masterson Gastrointestinal Eosinophilic Diseases Program, Department of Pediatrics, Digestive Health Institute, Children’s Hospital Colorado, University of Colorado School of Medicine, Aurora, CO 80045, USA; (J.C.M.); (C.M.-K.); (L.D.L.); (G.T.F.) GI and Liver Innate Immune Program, Department of Medicine, University of Colorado School of Medicine, Aurora, CO 80045, USA Allergy, Inflammation & Remodeling Research Laboratory, Kathleen Lonsdale Institute for Human Health Research, Department of Biology, Maynooth University, Maynooth, County Kildare, Ireland
Calies Menard-Katcher Gastrointestinal Eosinophilic Diseases Program, Department of Pediatrics, Digestive Health Institute, Children’s Hospital Colorado, University of Colorado School of Medicine, Aurora, CO 80045, USA; (J.C.M.); (C.M.-K.); (L.D.L.); (G.T.F.)
Leigha D. Larsen Gastrointestinal Eosinophilic Diseases Program, Department of Pediatrics, Digestive Health Institute, Children’s Hospital Colorado, University of Colorado School of Medicine, Aurora, CO 80045, USA; (J.C.M.); (C.M.-K.); (L.D.L.); (G.T.F.)
Glenn T. Furuta Gastrointestinal Eosinophilic Diseases Program, Department of Pediatrics, Digestive Health Institute, Children’s Hospital Colorado, University of Colorado School of Medicine, Aurora, CO 80045, USA; (J.C.M.); (C.M.-K.); (L.D.L.); (G.T.F.) GI and Liver Innate Immune Program, Department of Medicine, University of Colorado School of Medicine, Aurora, CO 80045, USA
Lisa A. Spencer Gastrointestinal Eosinophilic Diseases Program, Department of Pediatrics, Digestive Health Institute, Children’s Hospital Colorado, University of Colorado School of Medicine, Aurora, CO 80045, USA; (J.C.M.); (C.M.-K.); (L.D.L.); (G.T.F.) GI and Liver Innate Immune Program, Department of Medicine, University of Colorado School of Medicine, Aurora, CO 80045, USA Correspondence: ; Tel.: +1-303-724-3277

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Sciumè GD, Visaggi P, Sostilio A, Tarducci L, Pugno C, Frazzoni M, Ricchiuti A, Bellini M, Giannini EG, Marchi S, Savarino V, de Bortoli N. Eosinophilic esophagitis: novel concepts regarding pathogenesis and clinical manifestations. Minerva Gastroenterol (Torino) 2021;68:23-39. [PMID: 33435660 DOI: 10.23736/s2724-5985.20.02807-x] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]

Relationship of the Esophageal Microbiome and Tissue Gene Expression and Links to the Oral Microbiome: A Randomized Clinical Trial. Clin Transl Gastroenterol 2020;11:e00235. [PMID: 33512805 PMCID: PMC7721221 DOI: 10.14309/ctg.0000000000000235] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open

Doyle AD, Masuda MY, Kita H, Wright BL. Eosinophils in Eosinophilic Esophagitis: The Road to Fibrostenosis is Paved With Good Intentions. Front Immunol 2020;11:603295. [PMID: 33335531 PMCID: PMC7736408 DOI: 10.3389/fimmu.2020.603295] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2020] [Accepted: 11/03/2020] [Indexed: 12/15/2022] Open

Rieder E, Fernandez-Becker NQ, Sarosiek J, Guillaume A, Azagury DE, Clarke JO. Achalasia: physiology and diagnosis. Ann N Y Acad Sci 2020;1482:85-94. [PMID: 33140485 DOI: 10.1111/nyas.14510] [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: 05/15/2020] [Revised: 09/17/2020] [Accepted: 09/22/2020] [Indexed: 12/18/2022]

Chen JW. Management of Eosinophilic Esophagitis: Dietary and Nondietary Approaches. Nutr Clin Pract 2020;35:835-847. [PMID: 32822071 DOI: 10.1002/ncp.10571] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open

Oliva S, Azouz NP, Stronati L, Rothenberg ME. Recent advances in potential targets for eosinophilic esophagitis treatments. Expert Rev Clin Immunol 2020;16:421-428. [PMID: 32163308 DOI: 10.1080/1744666x.2020.1742110] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]

Upparahalli Venkateshaiah S, Niranjan R, Manohar M, Verma AK, Kandikattu HK, Lasky JA, Mishra A. Attenuation of Allergen-, IL-13-, and TGF-α-induced Lung Fibrosis after the Treatment of rIL-15 in Mice. Am J Respir Cell Mol Biol 2020;61:97-109. [PMID: 30702923 DOI: 10.1165/rcmb.2018-0254oc] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open

Abstract

Endogenous IL-15 deficiency promotes lung fibrosis; therefore, we examined the effect of induced IL-15 in restricting the progression of lung fibrosis. Our objective in this work was to establish a novel therapeutic molecule for pulmonary fibrosis. Western blot, qPCR, and ELISA were performed on the lung tissues of IL-15-deficient mice, and recombinant IL-15 (rIL-15)-treated CC10-IL-13 and CC10-TGF-α mice, and allergen-challenged CC10-IL-15 mice were examined to establish the antifibrotic effect of IL-15 in lung fibrosis. We show that endogenous IL-15 deficiency induces baseline profibrotic cytokine and collagen accumulation in the lung, and pharmacological delivery of rIL-15 downregulates Aspergillus antigen-induced lung collagen, the profibrotic cytokines IL-13 and TGF-β1, and α-SMA⁺ and FSP1⁺ cells in mice. To confirm that overexpression of IL-15 diminishes pulmonary fibrosis, we generated CC10-rtTA-tetO7-IL-15 transgenic mice and challenged them with Aspergillus antigen. Aspergillus antigen-challenged, doxycycline (DOX)-treated CC10-IL-15 transgenic mice exhibited decreased collagen accumulation, profibrotic cytokine (IL-13 and TGF-β1) expression, and α-SMA⁺ and FSP1⁺ cells compared with IL-15-overexpressing mice not treated with DOX. Additionally, to establish that the antifibrotic effect of IL-15 is not limited to allergen-induced fibrosis, we showed that rIL-15 or IL-15 agonist treatment restricted pulmonary fibrosis even in CC10-IL-13 and CC10-TGF-α mice. Mechanistically, we show that T-helper cell type 17 suppressor IL-15-responsive RORγ⁺ T regulatory cells are induced in DOX-treated, allergen-challenged IL-15-overexpressing mice, which may be a novel pathway for restricting progression of pulmonary fibrosis. Taken together, our data establishes antifibrotic activity of IL-15 that might be a novel therapeutic molecule to combat the development of pulmonary fibrosis.

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Unique IL-13Rα2/STAT3 mediated IL-13 regulation detected in lung conventional dendritic cells, 24 h post viral vector vaccination. Sci Rep 2020;10:1017. [PMID: 31974500 PMCID: PMC6978450 DOI: 10.1038/s41598-020-57815-z] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2019] [Accepted: 12/30/2019] [Indexed: 12/19/2022] Open

Votto M, Marseglia GL, De Filippo M, Brambilla I, Caimmi SME, Licari A. Early Life Risk Factors in Pediatric EoE: Could We Prevent This Modern Disease? Front Pediatr 2020;8:263. [PMID: 32548083 PMCID: PMC7274037 DOI: 10.3389/fped.2020.00263] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2020] [Accepted: 04/27/2020] [Indexed: 12/15/2022] Open

Silva FMDCE, Oliveira EED, Ambrósio MGE, Ayupe MC, Souza VPD, Gameiro J, Reis DRDL, Machado MA, Macedo GC, Mattes J, Ferreira AP. High-fat diet-induced obesity worsens TH2 immune response and immunopathologic characteristics in murine model of eosinophilic oesophagitis. Clin Exp Allergy 2019;50:244-255. [PMID: 31837231 DOI: 10.1111/cea.13533] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2019] [Revised: 10/11/2019] [Accepted: 11/04/2019] [Indexed: 12/12/2022]

Shaverdashvili K, Padlo J, Weinblatt D, Jia Y, Jiang W, Rao D, Laczkó D, Whelan KA, Lynch JP, Muir AB, Katz JP. KLF4 activates NFκB signaling and esophageal epithelial inflammation via the Rho-related GTP-binding protein RHOF. PLoS One 2019;14:e0215746. [PMID: 30998758 PMCID: PMC6472825 DOI: 10.1371/journal.pone.0215746] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2018] [Accepted: 04/08/2019] [Indexed: 12/12/2022] Open

Arias Á, Lucendo AJ. Molecular basis and cellular mechanisms of eosinophilic esophagitis for the clinical practice. Expert Rev Gastroenterol Hepatol 2019;13:99-117. [PMID: 30791784 DOI: 10.1080/17474124.2019.1546120] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]

Kutty GR, Downs-Kelly E, Crispin HT, Peterson KA. Elevated Tryptase in EoE Is an Independent Phenomenon Associated with Extra-Esophageal Symptoms. Dig Dis Sci 2019;64:152-157. [PMID: 30267171 DOI: 10.1007/s10620-018-5298-7] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2018] [Accepted: 09/19/2018] [Indexed: 12/14/2022]

Abstract

BACKGROUND

Eosinophilic esophagitis (EoE) is a chronic disease characterized histologically by > 15 eosinophils per high-power field (eos/hpf). Esophageal mucosal mast cells have been implicated in EoE pathogenesis. The association of atopy with EoE has been established but has not been correlated with levels of serum tryptase. The lack of concurrent atopy in some patients suggests the possibility that atopy may either be the related subtype of EoE or may be a sign of comorbidities. No study has looked at whether patients present with different phenotypes/comorbid disease when they have evidence of elevated serum tryptase. We hypothesized that these patients differ with respect to presentation and comorbidities with more refractory GI disease.

AIMS

To examine whether elevations of serum tryptase associate with different, more severe clinical presentations in EoE patients which may be explained via mast cell activation.

MATERIALS AND METHODS

Retrospective chart review identified 72 patients with EoE with results for serum tryptase between 2015 and 2016. Patients were classified as Tryptase^HI (tryptase > 10.9 µg/l) and Tryptase^LO (< 10.9 µg/l). Clinical characteristics and treatment response were compared using univariate analysis and multivariate regression between the groups.

RESULTS

Out of 72 patients, 12 were tested as Tryptase^HI (16.7%, 95% CI 8.1-25.3%). Tryptase^HI was associated frequently with asthma (P = 0.0003), urticaria (P = 0.002), arthralgia (P = 0.005), sinusitis (P = 0.03), nausea/vomiting (P = 0.046), and eosinophilic gastrointestinal disease (P = 0.001). Asthma and arthralgia were found to be significantly associated with Tryptase^HI (P = 0.0013, P = 0.0098, respectively). Mucosal eosinophil counts and tryptase levels were not correlated (R² 0.095, P = 0.77). Tryptase did not resolve with resolution of esophageal eosinophilia.

CONCLUSIONS

We found that EoE patients with elevated tryptase levels more commonly presented with asthma, urticaria, arthralgia, nausea/vomiting, sinusitis, and more distal eosinophilia. This indicates that atopy in EoE patients warrants further exploration. The lack of correlation between histologic remission and reduction of serum tryptase levels post-treatment suggests that mast cell activation may be an independent, yet associated disease. More study into this unique association is warranted.

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Spechler SJ. Eosinophilic esophagitis: novel concepts regarding pathogenesis and clinical manifestations. J Gastroenterol 2019;54:837-844. [PMID: 31342146 PMCID: PMC6759606 DOI: 10.1007/s00535-019-01604-7] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2019] [Accepted: 07/09/2019] [Indexed: 02/07/2023]

Muir AB, Wang JX, Nakagawa H. Epithelial-stromal crosstalk and fibrosis in eosinophilic esophagitis. J Gastroenterol 2019;54:10-18. [PMID: 30101408 PMCID: PMC6314980 DOI: 10.1007/s00535-018-1498-3] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2018] [Accepted: 07/29/2018] [Indexed: 02/07/2023]

Spechler SJ, Konda V, Souza R. Can Eosinophilic Esophagitis Cause Achalasia and Other Esophageal Motility Disorders? Am J Gastroenterol 2018;113:1594-1599. [PMID: 30315308 DOI: 10.1038/s41395-018-0240-3] [Citation(s) in RCA: 57] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2018] [Accepted: 07/20/2018] [Indexed: 12/11/2022]

Dellon ES, Selitsky SR, Genta RM, Lash RH, Parker JS. Gene expression-phenotype associations in adults with eosinophilic esophagitis. Dig Liver Dis 2018;50:804-811. [PMID: 29628359 PMCID: PMC6059985 DOI: 10.1016/j.dld.2018.03.021] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2018] [Revised: 03/09/2018] [Accepted: 03/19/2018] [Indexed: 02/06/2023]

Lee H. Changing Concept of the Prevalence of Eosinophilic Esophagitis: Visible and Hidden Patients. Clin Endosc 2018;51:307-309. [PMID: 29969848 PMCID: PMC6078922 DOI: 10.5946/ce.2018.071] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2018] [Accepted: 05/16/2018] [Indexed: 12/19/2022] Open

Spergel JM, Aceves SS, Kliewer K, Gonsalves N, Chehade M, Wechsler JB, Groetch M, Friedlander J, Dellon ES, Book W, Hirano I, Muir AB, Cianferoni A, Spencer L, Liacouras CA, Cheng E, Kottyan L, Wen T, Platts-Mills T, Rothenberg ME. New developments in patients with eosinophilic gastrointestinal diseases presented at the CEGIR/TIGERS Symposium at the 2018 American Academy of Allergy, Asthma & Immunology Meeting. J Allergy Clin Immunol 2018;142:48-53. [PMID: 29803797 PMCID: PMC6129859 DOI: 10.1016/j.jaci.2018.05.005] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2018] [Revised: 05/17/2018] [Accepted: 05/18/2018] [Indexed: 12/28/2022]

Affiliation(s)

Jonathan M Spergel Division of Allergy and Immunology, Children's Hospital of Philadelphia, Philadelphia, Pa; Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pa
Seema S Aceves Division of Allergy, Immunology, Departments of Pediatrics and Medicine, University of California, San Diego, Rady Children's Hospital, San Diego, La Jolla, Calif
Kara Kliewer Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center and Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio
Nirmala Gonsalves Division of Gastroenterology and Hepatology, Northwestern University-Feinberg School of Medicine, Chicago, Ill
Mirna Chehade Mount Sinai Center for Eosinophilic Disorders, Icahn School of Medicine at Mount Sinai, New York, NY
Joshua B Wechsler Eosinophilic Gastrointestinal Diseases Program, Division of Gastroenterology, Hepatology, and Nutrition, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Ill
Marion Groetch Mount Sinai Center for Eosinophilic Disorders, Icahn School of Medicine at Mount Sinai, New York, NY
Joshua Friedlander Digestive Health Institute, Children's Hospital Colorado, and the Aerodigestive Program, University of Colorado School of Medicine, Aurora, Colo
Evan S Dellon Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, NC
Wendy Book American Partnership for Eosinophilic Disorders, Atlanta, Ga
Ikuo Hirano Division of Gastroenterology and Hepatology, Northwestern University-Feinberg School of Medicine, Chicago, Ill
Amanda B Muir Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pa; Division of Gastroenterology and Nutrition, Children's Hospital of Philadelphia, Philadelphia, Pa
Antonella Cianferoni Division of Allergy and Immunology, Children's Hospital of Philadelphia, Philadelphia, Pa; Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pa
Lisa Spencer Beth Israel Deaconess, Boston, Mass
Chris A Liacouras Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pa; Division of Gastroenterology and Nutrition, Children's Hospital of Philadelphia, Philadelphia, Pa
Edaire Cheng Departments of Pediatrics and Internal Medicine, Children's Medical Center, University of Texas Southwestern Medical Center, Dallas, Tex
Leah Kottyan Center for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center and Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio
Ting Wen Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center and Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio
Thomas Platts-Mills Division of Asthma, Allergy, and Immunology, University of Virginia, Charlottesville, Va
Marc E Rothenberg Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center and Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio.

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Eosinophilic Esophagitis in Children and Adults. Gastrointest Endosc Clin N Am 2018;28:59-75. [PMID: 29129300 DOI: 10.1016/j.giec.2017.07.004] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]

Eden K, Rothschild DE, McDaniel DK, Heid B, Allen IC. Noncanonical NF-κB signaling and the essential kinase NIK modulate crucial features associated with eosinophilic esophagitis pathogenesis. Dis Model Mech 2017;10:1517-1527. [PMID: 29259025 PMCID: PMC5769607 DOI: 10.1242/dmm.030767] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2017] [Accepted: 10/25/2017] [Indexed: 12/16/2022] Open