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Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 21, 2015; 21(43): 12283-12295
Published online Nov 21, 2015. doi: 10.3748/wjg.v21.i43.12283
Th17 plasticity and its changes associated with inflammatory bowel disease
Aito Ueno, Abhisek Ghosh, Daniel Hung, Ji Li, Humberto Jijon
Aito Ueno, Daniel Hung, Humberto Jijon, Department of Medicine, University of Calgary, Calgary T2N 1N4, Alberta, Canada
Abhisek Ghosh, Darent Valley Hospital, Dartford, DA2 8DA Kent, United Kingdom
Ji Li, Department of Gastroenterology, Peking Union Hospital, Beijing 100730, China
Author contributions: The listed authors solely contributed to this manuscript in writing and searching the literatures
Conflict-of-interest statement: The authors have no conflict of interest to report in this work.
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:
Correspondence to: Dr. Aito Ueno, Department of Medicine, University of Calgary, HSC1838, 2500 University Dr. NW, Calgary T2N 1N4, Alberta, Canada.
Telephone: +1-403-2206603 Fax: +1-403-2109157
Received: June 23, 2015
Peer-review started: June 26, 2015
First decision: July 20, 2015
Revised: August 17, 2015
Accepted: October 23, 2015
Article in press: October 26, 2015
Published online: November 21, 2015

CD4 T helper (Th) cell differentiation into distinct T cell subsets is critical to the normal function of the immune system. Until recently, the paradigm held that naïve T cells differentiated into distinct subsets under the guidance of environmental cues (e.g., cytokines) and that once polarized, these cells were committed to a particular functional state. However, the existence of transdifferentiated T cell populations, which express signature transcription factors and cytokines associated with more than one Th subset, challenges the immutability of T helper subsets and suggests that plasticity is a feature of multifaceted immune responses. How this process impacts immune dysregulation in diseases such as inflammatory bowel diseases (IBD) and the machinery that underlies this process is far from fully understood. Interleukin (IL)-17 secreting helper T (Th17) cells have been heavily implicated in tissue-specific immune pathology including murine models of IBD, human Crohn’s disease and ulcerative colitis. Plasticity within this subset is suggested by the existence of IL-17 secreting cells, which, can also secrete interferon-γ, the signature cytokine for Th1 cells or, can co-express the anti-inflammatory transcription factor forkhead box p3, a signature transcription factor of regulatory T cells. In this review we mainly discuss evidence for Th17 plasticity, mechanisms, which govern it, and highlight the potential to therapeutically target this process in human IBD.

Keywords: Th7, Regulatory T cells, T cell plasticity, Inflammatory bowel disease

Core tip: Recently, two innovative clinical failures in inflammatory bowel disease which sought to manipulate T helper (Th) subsets via either transplantation of regulatory T cells or interleukin-17 blockade using secukinumab, suggest that altering the balance between inflammatory and regulatory subsets in inflammatory bowel diseases (IBD) may be more complex than previously thought. One reason may be the flexible nature of T helper subset commitment, otherwise referred to as plasticity. Here we discuss plasticity between regulatory and inflammatory subsets in T helper CD4+ cells, especially Th17 cell subset, and the potential to therapeutically target this process in human IBD.