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Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 21, 2016; 22(3): 974-995
Published online Jan 21, 2016. doi: 10.3748/wjg.v22.i3.974
Disrupted regulatory T cell homeostasis in inflammatory bowel diseases
Christophe Pedros, Fanny Duguet, Abdelhadi Saoudi, Marianne Chabod
Christophe Pedros, Division of Cell Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92307, United States
Fanny Duguet, Abdelhadi Saoudi, UMR Inserm, U1043, F-31300 Toulouse, France
Fanny Duguet, Abdelhadi Saoudi, UMR CNRS, U5282, F-31300 Toulouse, France
Fanny Duguet, Abdelhadi Saoudi, Université de Toulouse, UPS, Centre de Physiopathologie de Toulouse Purpan, F-31300 Toulouse, France
Marianne Chabod, Epidermis Differentiation and Rheumatoid Autoimmunity Laboratory, UMR CNRS 5165, INSERM U 1056, Toulouse III University, F-31300 Toulouse, France
Author contributions: Pedros C, Duguet F, Saoudi A and Chabod M analyzed the literature and wrote the manuscript.
Supported by INSERM, Fondation pour la Recherche Médicale No.DEQ2000326531 and Région Midi-Pyrénées; Saoudi A is supported by the Centre National de la Recherche Scientifique.
Conflict-of-interest statement: The authors have no conflicts of interest to report.
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: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Marianne Chabod, PhD, Assistant Professor, Epidermis Differentiation and Rheumatoid Autoimmunity Laboratory, UMR CNRS 5165, INSERM U 1056, Toulouse III University, 118 Route de Narbonne, F-31300 Toulouse, France. marianne.chabod@udear.cnrs.fr
Telephone: +33-5611-58432 Fax: +33-5614-99036
Received: May 26, 2015
Peer-review started: May 29, 2015
First decision: September 9, 2015
Revised: October 2, 2015
Accepted: November 19, 2015
Article in press: November 19, 2015
Published online: January 21, 2016
Abstract

In the gut, where billions of non-self-antigens from the food and the microbiota are present, the immune response must be tightly regulated to ensure both host protection against pathogenic microorganisms and the absence of immune-related pathologies. It has been well documented that regulatory T cells (Tregs) play a pivotal role in this context. Indeed, Tregs are able to prevent excessive inflammation, which can lead to the rupture of intestinal homeostasis observed in inflammatory bowel diseases (IBDs). Both the worldwide incidence and prevalence of such diseases have increased throughout the latter part of the 20th century. Therefore, it is crucial to understand how Tregs suppress the colitogenic immune cells to establish new treatments for patients suffering from IBDs. In this review, we will first summarize the results obtained in animal model studies that highlight the importance of Tregs in maintaining intestinal homeostasis and describe the specific suppressive mechanisms involved. Next, our current knowledge about Tregs contribution to human IBDs will be reviewed, as well as the current therapeutic perspective on using Tregs for clinical IBD treatment and the challenges that remain to be resolved to ensure both the safety and effectiveness of these therapies in targeting this critical immune-regulatory cell population.

Keywords: Regulatory T cells, Foxp3, Gut, Inflammatory bowel disease, Colitis

Core tip: The mucosal immune system must be very well-controlled to avoid immune responses against both microbial and innocuous food antigens. Regulatory T cells (Tregs) constitute a key mechanism to ensure gut homeostasis. In this review, both Treg biology and the suppressive mechanisms that have been identified using animal models of intestinal inflammation are first summarized. Then, we discuss the current knowledge concerning their contribution to human inflammatory bowel diseases (IBDs). Interestingly, these relatively recent advances have led to new therapeutic perspectives for IBD treatment by targeting this potent immunosuppressive cell population.