Generation of pathogenic T(H)17 cells in the absence of TGF-β signalling.
Generation of pathogenic T(H)17 cells in the absence of TGF-β signalling.
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作者：
选择性产生白细胞介素（IL）-17的CD 4 + T细胞对宿主防御和自身免疫至关重要。IL-23在体内对辅助性T细胞17（Th 17）至关重要，它被认为不能驱动初始分化。相反，IL-6和转化生长因子（TGF）-β1被认为是启动特化的因素。在此，我们表明，Th 17分化可以发生在TGF-β信号转导的情况下。单独使用IL-6和IL-23均不能有效地产生Th 17细胞;然而，这些细胞因子与IL-1β联合使用可有效地诱导幼稚前体细胞产生IL-17，而不依赖于TGF-β。Il 17 a/Il 17 f和Rorc启动子的表观遗传修饰在没有TGF-β1的情况下进行，允许产生共表达Rorγt和T-bet的细胞。T-bet+ Rorγt+ Th 17细胞在实验性变态反应性脑脊髓炎（EAE）中体内产生，并且在没有TGF-β1的情况下用IL-23产生的过继转移的Th 17细胞在该疾病模型中是致病性的。这些数据表明Th 17分化的替代模式。与将IL-23 R与自身免疫联系起来的遗传数据一致，我们的发现再次强调了IL-23的重要性，因此可能具有治疗意义。
CD4+ T cells that selectively produce interleukin (IL)-17, are critical for host defense and autoimmunity. Crucial for T helper17 (Th17) cells in vivo, IL-23 has been thought to be incapable of driving initial differentiation. Rather, IL-6 and transforming growth factor (TGF)-β1 have been argued to be the factors responsible for initiating specification. Herein, we show that Th17 differentiation can occur in the absence of TGF-β signaling. Neither IL-6 nor IL-23 alone efficiently generated Th17 cells; however, these cytokines in combination with IL-1β effectively induced IL-17 production in naïve precursors, independently of TGF-β. Epigenetic modification of the Il17a/Il17f and Rorc promoters proceeded without TGF-β1, allowing the generation of cells that co-expressed Rorγt and T-bet. T-bet+ Rorγt+ Th17 cells are generated in vivo during experimental allergic encephalomyelitis (EAE), and adoptively transferred Th17 cells generated with IL-23 without TGF-β1 were pathogenic in this disease model. These data suggest an alternative mode for Th17 differentiation. Consistent with genetic data linking IL23R with autoimmunity, our findings re-emphasize the importance of IL-23 and therefore have may have therapeutic implications.
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影响因子：
64.5
作者：
Ivanov, Ivaylo I.;McKenzie, Brent S.;Littman, Dan R.
通讯作者：
Littman, Dan R.
影响因子：
30.5
作者：
Acosta-Rodriguez, Eva V.;Napolitani, Giorgio;Sallusto, Federica
通讯作者：
Sallusto, Federica
影响因子：
64.8
作者：
Bettelli, E;Carrier, YJ;Kuchroo, VK
通讯作者：
Kuchroo, VK
T-BET的丧失，但不是STAT1阻止了实验性自身免疫性脑脊髓炎的发展。
影响因子：
15.3
作者：
Bettelli, E;Sullivan, B;Szabo, SJ;Sobel, RA;Glimcher, H;Kuchroo, VK
通讯作者：
Kuchroo, VK
影响因子：
30.5
作者：
Gutcher, Ilona;Urich, Eduard;Becher, Burkhard
通讯作者：
Becher, Burkhard