IL-6 programs TH-17 cell differentiation by promoting sequential engagement of the IL-21 and IL-23 pathways

Speaker: 鄭元鈞                              Time:  September 26, 2007

Commentator: 黎煥耀 教授                    Place:  Room 601

Abstract

TH-17 cell, the IL-17-producing T cell, has recently been classified as a new effector T-cell subset distinct from Th1 and Th2 cells.  TH-17 cell has been considered to have a critical role in autoimmune disease, including Crohn's disease and psoriasis.  However, the mechanism of TH-17 cell differentiation and expansion is not clear.  Several cytokines have been found to participate in the differentiation of naïve T cells toward the TH-17 cell lineage.  Previous studies showed that the differentiation of TH-17 cells required IL-6, IL-21, IL-23 and TGF-β.  Besides, the orphan nuclear receptor RORγt, which is induced by IL-6 and TGF-β, is required and sufficient for the expression of IL-17.  In this paper the authors attempted to search for the relation between these cytokine and TH-17 cell differentiation.  They demonstrate that (1) IL-6 can induce IL-21 and IL-23R expression in CD4+ T cells.  (2) IL-21 can be amplified by itself through an autocrine process and then induce RORγt and IL-17 expression through IL-23-IL-23R signaling.  (3) The IL-6 and IL-21 induced signal pathway required both STAT3 and RORγt to induce maximum IL-17 expression.  Therefore, the author constructed a plausible mechanism for TH-17 cell differentiation.  IL-6 induced IL-21 to orchestrate a series of downstream cytokine-dependent signaling pathways in concert with TGF-β to amplify RORγt-dependent differentiation of TH-17 cells.

Reference

(1)Development, cytokine profile and function of human interleukin 17–producing helper T cells.  Wilson NJ, Boniface K, ..., Bowman EP, de Waal Malefyt R Nat Immunol 2007 Sep 8(9):950-7

(2)T cell-produced transforming growth factor-beta1 controls T cell tolerance and regulates Th1- and Th17-cell differentiation.
Li MO, Wan YY, Flavell RA Immunity 2007 May 26(5):579-91