Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.
J Immunol. 2013 Apr 1;190(7):3049-53. doi: 10.4049/jimmunol.1203032. Epub 2013 Feb 27.
Bcl6 is required for CD4 T cell differentiation into T follicular helper cells (Tfh). In this study, we examined the role of IL-6 in early processes of in vivo Tfh differentiation, because the timing and mechanism of action of IL-6 in Tfh differentiation have been controversial in vivo. We found that early Bcl6(+)CXCR5(+) Tfh differentiation was severely impaired in the absence of IL-6; however, STAT3 deficiency failed to recapitulate that defect. IL-6R 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 cell 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.
Bcl6 对于 CD4 T 细胞分化为滤泡辅助性 T 细胞（Tfh）是必需的。在这项研究中，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 分化中的作用时间和机制在体内一直存在争议。我们发现，在缺乏 IL-6 的情况下，早期 Bcl6(+)CXCR5(+)Tfh 分化严重受损；然而，STAT3 缺陷不能重现该缺陷。IL-6R 信号在 CD4 T 细胞中特异性激活转录因子 STAT1。令人惊讶的是，我们发现 STAT1 活性是体内 Bcl6 诱导和早期 Tfh 分化所必需的。IL-6 介导的 STAT3 激活对于下调 IL-2Rα 以限制急性病毒感染中的 Th1 细胞分化很重要。因此，IL-6 信号是 Tfh 分化程序的主要早期诱导剂，出乎意料的是，该过程由 STAT3 和 STAT1 转录因子共同介导。
