-17 cell differentiation by promoting sequential engagement of the IL-21 and IL-23 pathways
摘要：
T helper cells that produce interleukin 17 (IL-17; 'T-17 cells') are a distinct subset of proinflammatory cells whosefunction requires IL-23 but whosedifferentiation requires only IL-6 and transforming growth factor-β (TGF-β). 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 CD4T cells. Both IL-21 and IL-23, along with TGF-β, 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-17 cells. IL-21 and IL-23 induced the orphan nuclear receptor RORγt, 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-β, amplify RORγt-dependent differentiation of T-17 cells.
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DOI：
10.1016/j.nimb.2008.03.077
被引量：
Elsevier
Taylor & Francis
BMJ
Nature
Springer
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