Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 14, 2017; 23(42): 7505-7518
Published online Nov 14, 2017. doi: 10.3748/wjg.v23.i42.7505
Intestinal epithelium, intraepithelial lymphocytes and the gut microbiota - Key players in the pathogenesis of celiac disease
Bożena Cukrowska, Agnieszka Sowińska, Joanna Beata Bierła, Elżbieta Czarnowska, Anna Rybak, Urszula Grzybowska-Chlebowczyk
Bożena Cukrowska, Agnieszka Sowińska, Joanna Beata Bierła, Elżbieta Czarnowska, Department of Pathology, The Children’s Memorial Health Institute, Warsaw 04-730, Poland
Anna Rybak, Department of Gastroenterology, Division of Neurogastroenterology and Motility, Great Ormond Street Hospital, London WC1N 3JH, United Kingdom
Urszula Grzybowska-Chlebowczyk, Department of Pediatrics, School of Medicine, Medical University of Silesia, Katowice, 40-752, Poland
Author contributions: Cukrowska B conceived and designed the study, and drafted and reviewed the manuscript; Sowińska A conceived the study, reviewed the literature, made the figures, and drafted the manuscript; Czarnowska E, Bierła J and Grzybowska-Chlebowczyk U reviewed the literature and drafted the manuscript; Rybak A drafted and reviewed the manuscript; all authors read and approved the manuscript.
Conflict-of-interest statement: The authors declare no conflicts of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Supported by the Children’s Memorial Health Institute Grants, No. 236/15, No. 243/16 and No. S147/2016.
Correspondence to: Bożena Cukrowska, MD, Professor, PhD, Department of Pathology, Laboratory of Immunology, The Children’s Memorial Health Institute, Aleja Dzieci Polskich 20, 04-730 Warsaw, Poland.
Telephone: +48-2281-51091 Fax: +48-22815-1960
Received: May 22, 2017
Peer-review started: May 23, 2017
First decision: June 23, 2017
Revised: July 31, 2017
Accepted: August 15, 2017
Article in press: August 15, 2017
Published online: November 14, 2017

Celiac disease (CD) is a chronic immune-mediated disorder triggered by the ingestion of gluten in genetically predisposed individuals. Before activating the immune system, gluten peptides are transferred by the epithelial barrier to the mucosal lamina propria, where they are deamidated by intestinal tissue transglutaminase 2. As a result, they strongly bind to human leucocyte antigens (HLAs), especially HLA-DQ2 and HLA-DQ8, expressed on antigen-presenting cells. This induces an inflammatory response, which results in small bowel enteropathy. Although gluten is the main external trigger activating both innate and adaptive (specific) immunity, its presence in the intestinal lumen does not fully explain CD pathogenesis. It has been hypothesized that an early disruption of the gut barrier in genetically susceptible individuals, which would result in an increased intestinal permeability, could precede the onset of gluten-induced immune events. The intestinal barrier is a complex functional structure, whose functioning is dependent on intestinal microbiota homeostasis, epithelial layer integrity, and the gut-associated lymphoid tissue with its intraepithelial lymphocytes (IELs). The aim of this paper was to review the current literature and summarize the role of the gut microbiota, epithelial cells and their intercellular junctions, and IELs in CD development.

Keywords: Celiac disease, Intestinal microbiota, Epithelium, Intraepithelial lymphocytes, Intestinal barrier

Core tip: There is evidence that the host-microbiota homeostasis is disrupted in celiac disease (CD) patients. Dysbiosis, meaning an imbalance in the gut microbiota and its metabolome, may activate innate immunity leading to pro-inflammatory changes, which induces intraepithelial lymphocyte infiltration and epithelial barrier damage, ultimately resulting in increased transfer of gluten peptides and inflammatory activation leading to CD development. The intestinal microbiota also has a direct effect on the breakdown of gluten and formation of immunogenic peptides. As colonization of the gut with microorganisms may be dependent on genetic factors, future prophylactic strategies may focus on gut microbiota modulation in genetically predisposed infants.