A critical function for transforming growth factor-β, interleukin 23 and proinflammatory cytokines in driving and modulating human TH-17 responses
A critical function for transforming growth factor-β, interleukin 23 and proinflammatory cytokines in driving and modulating human TH-17 responses
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DOI：
10.1038/ni.1613
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发表时间：
2008-06-01
影响因子：
30.5
通讯作者：
Soumelis, Vassili
中科院分区：
文献类型：
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作者：
Volpe, Elisabetta;Servant, Nicolas;Soumelis, Vassili
产生白介素17(IL-17)的辅助性T细胞(T-H-17细胞)是一类不同于辅助性T细胞1型(T(H)1)和辅助性T(H)2细胞的辅助性T细胞亚群，在抗菌防御和自身免疫中具有独特的功能。导致人类T-H-17分化的因素仍然存在争议。采用实验和计算相结合的系统方法，我们在这里证明了转化生长因子-β、白介素23(IL-23)和促炎细胞因子(IL-1b和IL-6)都是人类T-H-17分化所必需的。然而，单个T-H-17细胞来源的细胞因子，如IL-17、IL-21、IL-22和IL-6，以及整个T-H-17细胞因子谱，都受到T-H-17促进细胞因子的不同调节。转化生长因子-β是至关重要的，它的缺失导致T-H-17图谱向T(H)1样图谱的转变。我们的结果为人类T-H-17分化的调控提供了新的线索，并为T辅助反应的全球分析提供了一个框架。
Interleukin 17 (IL-17)-producing T helper 17 cells (T-H-17 cells) have been described as a T helper cell subset distinct from T helper type 1 (T(H)1) and T(H)2 ells, with specific functions in antimicrobial defense and autoimmunity. The factors driving human T-H-17 differentiation remain controversial. Using a systematic approach combining experimental and computational methods, we show here that transforming growth factor-beta, interleukin 23 (IL-23) and proinflammatory cytokines (IL-1b and IL-6) were all essential for human T-H-17 differentiation. However, individual T-H-17 cell-derived cytokines, such as IL-17, IL-21, IL-22 and IL-6, as well as the global T-H-17 cytokine profile, were differentially modulated by T-H-17-promoting cytokines. Transforming growth factor-beta was critical, and its absence induced a shift from a T-H-17 profile to a T(H)1-like profile. Our results shed new light on the regulation of human T-H-17 differentiation and provide a framework for the global analysis of T helper responses.