IL-7 signalling represses Bcl-6 and the TFH gene program.
IL-7 signalling represses Bcl-6 and the TFH gene program.
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DOI：
10.1038/ncomms10285
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发表时间：
2016-01-08
影响因子：
16.6
通讯作者：
Oestreich KJ
中科院分区：
文献类型：
--
作者：
McDonald PW;Read KA;Baker CE;Anderson AE;Powell MD;Ballesteros-Tato A;Oestreich KJ
转录抑制因子 Bcl-6 与 CD4+ T 滤泡辅助细胞 (TFH) 和中央记忆 T (TCM) 细胞的发育有关。在这里，我们证明，作为对 IL-2 信号传导减弱的反应，辅助 T 1 (TH1) 细胞上调 Bcl-6 并共同启动 TFH 和 TCM 样基因程序，包括细胞因子受体 IL-6Rα 和 IL-7R 的表达。这种潜在的双能细胞群暴露于 IL-6 有利于 TFH 基因程序，而 IL-7 信号传导抑制 TFH 相关基因，包括 Bcl6 和 Cxcr5，但不抑制中药相关基因 Klf2 和 Sell。从机制上讲，IL-7 依赖性 STAT5 激活有助于 Bcl-6 抑制。重要的是，抗原特异性 IL-6Rα+IL-7R+ CD4+ T 细胞在流感感染后的较晚时间点从效应细胞群中出现。这些数据支持 IL-7 在抑制 TFH 基因程序中的新作用，并引发不同的调节机制，通过该机制，后效应 TH1 细胞可能有助于长期的细胞介导和体液免疫。 目前尚不完全清楚细胞因子如何影响 TH1 细胞分化为中央记忆 T (TCM) 和滤泡 T 辅助 (TFH) 细胞。作者在此表明，TH1 细胞可以共同启动 TFH 和 TCM 基因程序的表达，并且 IL-7 信号传导抑制 TFH 相关基因，但不抑制 TCM 相关基因。
The transcriptional repressor Bcl-6 is linked to the development of both CD4+ T follicular helper (TFH) and central memory T (TCM) cells. Here, we demonstrate that in response to decreased IL-2 signalling, T helper 1 (TH1) cells upregulate Bcl-6 and co-initiate TFH- and TCM-like gene programs, including expression of the cytokine receptors IL-6Rα and IL-7R. Exposure of this potentially bi-potent cell population to IL-6 favours the TFH gene program, whereas IL-7 signalling represses TFH-associated genes including Bcl6 and Cxcr5, but not the TCM-related genes Klf2 and Sell. Mechanistically, IL-7-dependent activation of STAT5 contributes to Bcl-6 repression. Importantly, antigen-specific IL-6Rα+IL-7R+ CD4+ T cells emerge from the effector population at late time points post influenza infection. These data support a novel role for IL-7 in the repression of the TFH gene program and evoke a divergent regulatory mechanism by which post-effector TH1 cells may contribute to long-term cell-mediated and humoral immunity. It remains incompletely understood how cytokines shape TH1 cell differentiation to central memory T (TCM) and follicular T helper (TFH) cells. Here the authors show that TH1 cells can co-initiate the expression of both TFH and TCM gene programs and that IL-7 signalling represses TFH-associated but not TCM-associated genes.