| Literature DB >> 17581537 |
Liang Zhou1, Ivaylo I Ivanov, Rosanne Spolski, Roy Min, Kevin Shenderov, Takeshi Egawa, David E Levy, Warren J Leonard, Dan R Littman.
Abstract
T helper cells that produce interleukin 17 (IL-17; 'T(H)-17 cells') are a distinct subset of proinflammatory cells whose in vivo function requires IL-23 but whose in vitro differentiation requires only IL-6 and transforming growth factor-beta (TGF-beta). We demonstrate here that IL-6 induced expression of IL-21 that amplified an autocrine loop to induce more IL-21 and IL-23 receptor in naive CD4(+) T cells. Both IL-21 and IL-23, along with TGF-beta, induced IL-17 expression independently of IL-6. The effects of IL-6 and IL-21 depended on STAT3, a transcription factor required for the differentiation of T(H)-17 cells in vivo. IL-21 and IL-23 induced the orphan nuclear receptor RORgammat, which in synergy with STAT3 promoted IL-17 expression. IL-6 therefore orchestrates a series of 'downstream' cytokine-dependent signaling pathways that, in concert with TGF-beta, amplify RORgammat-dependent differentiation of T(H)-17 cells.Entities:
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Year: 2007 PMID： 17581537 DOI： 10.1038/ni1488
Source DB: PubMed Journal: Nat Immunol ISSN： 1529-2908 Impact factor: 25.606