Stat3 and Stat4 direct development of IL-17-secreting Th cells
Stat3 and Stat4 direct development of IL-17-secreting Th cells
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DOI：
10.4049/jimmunol.178.8.4901
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发表时间：
2007-04-15
影响因子：
4.4
通讯作者：
Kaplan, Mark H.
中科院分区：
文献类型：
--
作者：
Mathur, Anubhav N.;Chang, Hua-Chen;Kaplan, Mark H.
分泌白细胞介素 - 17（IL - 17）的CD4(+) T细胞在炎症免疫反应中起关键作用。在体内和体外，白细胞介素 - 23（IL - 23）或转化生长因子β1（TGFβ1）加白细胞介素 - 6（IL - 6）可促进这些细胞的发育。尽管人们对这种炎症性辅助性T细胞（Th）亚群的兴趣日益增加，但对其发育所需的转录因子知之甚少。我们证明，信号转导及转录激活因子3（Stat3）是调控TGFβ1加IL - 6以及IL - 23刺激产生分泌IL - 17表型所必需的，也是TGFβ1加IL - 6诱导的细胞中维甲酸相关孤儿受体γt（RORγt）表达所必需的。此外，将组成性激活的Stat3通过逆转录病毒转导到分化的T细胞培养物中，可增强这些细胞产生IL - 17的能力。我们进一步表明，信号转导及转录激活因子4（Stat4）对IL - 23诱导的（但不是TGFβ1加IL - 6诱导的）分泌IL - 17细胞的发育是部分必需的，并且对IL - 23加IL - 18刺激产生IL - 17是绝对必需的。在这些分泌IL - 17亚群发育过程中对Stat3和Stat4的需求揭示了在促炎细胞类型产生过程中辅助性T细胞命运决定的其他机制。
IL-17-secreting CD4(+) T cells are critically involved in inflammatory immune responses. Development of these cells is promoted in vivo and in vitro by IL-23 or TGF beta 1 plus IL-6. Despite growing interest in this inflammatory Th subset, little is known about the transcription factors that are required for their development. We demonstrate that Stat3 is required for programming the TGF beta 1 plus IL-6 and IL-23-stimulated IL-17-secreting phenotype, as well as for ROR gamma t expression in TGF beta 1 plus IL-6-primed cells. Moreover, retroviral transduction of a constitutively active Stat3 into differentiating T cell cultures enhances IL-17 production from these cells. We further show that Stat4 is partially required for the development of IL-23-, but not TGF beta 1 plus IL-6-primed IL-17-secreting cells, and is absolutely required for IL-17 production in response to IL-23 plus IL-18. The requirements for Stat3 and Stat4 in the development of these IL-17-secreting subsets reveal additional mechanisms in Th cell fate decisions during the generation of proinflammatory cell types.