Cutting edge: STAT1 is required for IL-6-mediated Bcl6 induction for early follicular helper cell differentiation.

Cutting edge: STAT1 is required for IL-6-mediated Bcl6 induction for early follicular helper cell differentiation.
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DOI:
10.4049/jimmunol.1203032
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发表时间:
2013-04-01
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
通讯作者:
Crotty S
Crotty S
中科院分区:
其他
文献类型:
--
作者:
Choi YS;Eto D;Yang JA;Lao C;Crotty S

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Bcl 6是CD 4 T细胞分化为滤泡辅助细胞(Tfh)所必需的。在这里,我们研究了IL-6在体内Tfh分化的早期过程中的作用,因为IL-6在Tfh细胞分化中的作用的时间和机制在体内一直存在争议。我们发现,早期Bcl 6 + CXCR 5 + Tfh细胞分化严重受损,在IL-6的情况下,然而,STAT 3缺陷未能重演的缺陷。IL-6受体信号传导在CD 4 T细胞中特异性地激活转录因子STAT 1。引人注目的是,我们发现STAT 1活性是体内Bcl 6诱导和早期Tfh分化所必需的。IL-6介导的STAT 3活化对于下调IL-2 R α以限制急性病毒感染中的Th 1分化是重要的。因此,IL-6信号传导是Tfh分化程序的主要早期诱导物,其意外地由STAT 3和STAT 1转录因子介导。
Bcl6 is required for CD4 T cell differentiation into follicular helper cells (Tfh). Here, we examined the role of IL-6 in early processes of in vivo Tfh differentiation, as the timing and mechanism of action of IL-6 in Tfh cell differentiation has been controversial in vivo. We found that early Bcl6+CXCR5+ Tfh cell differentiation was severely impaired in the absence of IL-6; however, STAT3 deficiency failed to recapitulate that defect. IL-6 receptor signaling activates the transcription factor STAT1 specifically in CD4 T cells. Strikingly, we found that STAT1 activity was required for Bcl6 induction and early Tfh differentiation in vivo. IL-6 mediated STAT3 activation is important for downregulation of IL-2Rα to limit Th1 differentiation in an acute viral infection. Thus, IL-6 signaling is a major early inducer of the Tfh differentiation program unexpectedly mediated by both STAT3 and STAT1 transcription factors.
白介素21在控制慢性病毒感染中的至关重要作用。
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