TGF-beta induces IL-9 production from human Th17 cells.
TGF-beta induces IL-9 production from human Th17 cells.
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DOI：
10.4049/jimmunol.1000356
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发表时间：
2010-07-01
期刊：
影响因子：
--
通讯作者：
Hafler DA
中科院分区：
文献类型：
--
作者：
Beriou G;Bradshaw EM;Lozano E;Costantino CM;Hastings WD;Orban T;Elyaman W;Khoury SJ;Kuchroo VK;Baecher-Allan C;Hafler DA
IL-9的分泌，最初被认为是一种Th 2细胞因子，最近被归因于一种新的CD 4 T细胞亚群称为Th 9在鼠系统。然而，IL-9也可以由小鼠Th 17细胞分泌，并且可以介导Th 17细胞的促炎活性方面。在这里，我们报告了IL-9是由人幼稚CD 4 T细胞分泌的，以响应Th 9（TGF-β和IL-4）或Th 17极化条件下的分化。然而，这些分化的幼稚细胞不共表达IL-17和IL-9，除非它们在Th 17分化诱导条件下反复刺激。与幼稚细胞相反，通过在刺激期间简单地提供TGF-β来诱导记忆CD 4 T细胞分泌IL-9，因为既不需要IL-4也不需要促炎细胞因子。此外，向诱导记忆细胞分泌IL-17的Th 17诱导细胞因子（IL-1β、IL-6、IL-21、IL-23）中添加TGF-β，导致IL-9在产生IL-17的记忆细胞中显著共表达。介导IL-9和IL-17的TGF-β依赖性共表达的促炎细胞因子被鉴定为IL-1β。此外，循环单核细胞是Th 17细胞通过其分泌IL-1β的能力产生IL-9的有效共刺激因子。最后，为了确定IL-9/IL-17共产生的CD 4细胞是否在炎症条件下发生改变，我们检查了自身免疫性糖尿病患者，并证明这些受试者表现出更高频率的记忆CD 4细胞，具有转化为IL-9+IL-17+细胞的能力。这些数据表明存在由IL-1β诱导的IL-17+IL-9+ CD 4细胞，其可能在人类自身免疫性疾病中起作用。
The secretion of IL-9, initially recognized as a Th2 cytokine, was recently attributed to a novel CD4 T cell subset termed Th9 in the murine system. However, IL-9 can also be secreted by mouse Th17 cells and may mediate aspects of the proinflammatory activities of Th17 cells. Here we report that IL-9 is secreted by human naive CD4 T cells in response to differentiation by Th9 (TGF-β and IL-4) or Th17 polarizing conditions. Yet, these differentiated naive cells did not coexpress IL-17 and IL-9, unless they were repeatedly stimulated under Th17 differentiation-inducing conditions. In contrast to the naive cells, memory CD4 T cells were induced to secrete IL-9 by simply providing TGF-β during stimulation, as neither IL-4 nor proinflammatory cytokines were required. Furthermore, the addition of TGF-β to the Th17-inducing cytokines (IL-1β, IL-6, IL-21, IL-23) that induce memory cells to secrete IL-17, resulted in the marked coexpression of IL-9 in IL-17 producing memory cells. The proinflammatory cytokine mediating TGF-β–dependent coexpression of IL-9 and IL-17 was identified to be IL-1β. Moreover, circulating monocytes were potent costimulators of IL-9 production by Th17 cells via their capacity to secrete IL-1β. Finally, to determine whether IL-9/IL-17 coproducing CD4 cells were altered in an inflammatory condition, we examined patients with autoimmune diabetes and demonstrated that these subjects exhibit a higher frequency of memory CD4 cells with the capacity to transition into IL-9+IL-17+ cells. These data demonstrate the presence of IL-17+IL-9+ CD4 cells induced by IL-1β that may play a role in human autoimmune disease.
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影响因子：
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作者：
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通讯作者：
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