Th17 plasticity and its relevance to inflammatory bowel disease

Research output: Contribution to journalReview article

Authors

  • Aito Ueno
  • Taku Kobayashi
  • Toshifumi Hibi
  • Humberto Jijon

Colleges, School and Institutes

External organisations

  • Department of Medicine, University of Calgary, Calgary, Alberta, T2N 1N4, Canada; Center for Advanced IBD Research and Treatment, Kitasato Institute Hospital, Minato-ku Shirokane 5-9-1 Tokyo, Japan. Electronic address: aueno@ucalgary.ca.
  • Institute of Translational Medicine and NIHR Biomedical Research Centre, University of Birmingham, Birmingham, UK.
  • Center for Advanced IBD Research and Treatment, Kitasato Institute Hospital, Minato-ku Shirokane 5-9-1 Tokyo, Japan.
  • Department of Medicine, University of Calgary, Calgary, Alberta, T2N 1N4, Canada.

Abstract

It is now clear that previously polarized T cells possess the ability to change their phenotype and repolarize towards different fates. This intrinsic flexibility is commonly referred to as plasticity and is influenced by the cytokine milieu, microbial products and products of metabolism which, in turn, regulate transcription factors and epigenetic machinery in the intestinal lamina propria. The intestinal immune system faces a particularly difficult challenge. It serves to protect the largest mucosal surface against infection and injury while maintaining a state of tolerance towards dietary antigens and the largest population of commensal organisms in the body. This requires a delicate balance between regulatory and effector T cells; loss of this balance is thought to lead to the development of Crohn's disease (CD) and ulcerative colitis (UC), collectively referred to as inflammatory bowel disease (IBD). These unique immune-mediated inflammatory diseases are directed not at self-antigens but rather at the commensal microorganisms which reside within the gut lumen. However, it is thought that owing to persistence of these microbial antigens, intestinal damage and systemic inflammation ensue. New data from mouse models of IBD suggest that T cell plasticity, particularly along the Th1-Th17 and Th17-Treg axes, plays an important role in the regulation of intestinal immune responses. Furthermore, patients with IBD demonstrate increased numbers of "transdifferentiated" T cell populations suggestive of heightened plasticity. This review will consider the mechanisms and roles of Th17 plasticity in the pathogenesis of IBD.

Details

Original languageEnglish
Pages (from-to)38-49
JournalJournal of Autoimmunity
Volume87
Early online date28 Dec 2017
Publication statusPublished - Feb 2018

Keywords

  • Journal Article, Review