Published online Nov 21, 2015. doi: 10.3748/wjg.v21.i43.12283
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.
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.