Bach2 Controls T Follicular Helper Cells by Direct Repression of Bcl-6
Bach2 Controls T Follicular Helper Cells by Direct Repression of Bcl-6
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DOI：
10.4049/jimmunol.1801400
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发表时间：
2019-04-15
影响因子：
4.4
通讯作者：
Hutloff, Andreas
中科院分区：
文献类型：
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作者：
Lahmann, Annette;Kuhrau, Julia;Hutloff, Andreas
T滤泡辅助性T细胞(TFH细胞)是一种特殊的T细胞亚群，在生发中心(GC)反应中调节B细胞长时间产生高度特异的抗体。然而，支持TFH细胞表型和功能的转录网络仍然不完全清楚。在这项研究中，我们确定转录因子Bach2是TFH细胞的中心负调控因子。Bach2在小鼠Tfh细胞中的异位过表达导致其表型的迅速丧失和随后的GC反应的崩溃。低水平的Bach2表达是维持标志性细胞因子IL-21、共抑制受体TIGIT和转录抑制因子Bcl-6高表达所必需的。与GC B细胞中的调控网络形成鲜明对比的是，Bach2在Tfh细胞中并不与Bcl6高水平共表达以抑制拮抗因子Blimp-1，但通过直接与启动子结合来抑制Bcl6。这些数据表明，通过取代BATF和IRF-4的激活复合体，Bach2以不同的方式调节Tfh细胞的转录网络，就像在GC B细胞中一样。
T follicular helper (Tfh) cells are a specialized T cell subset that regulates the long-lived production of highly specific Abs by B cells during the germinal center (GC) reaction. However, the transcriptional network sustaining the Tfh cell phenotype and function is still incompletely understood. In this study, we identify the transcription factor Bach2 as a central negative regulator of Tfh cells. Ectopic overexpression of Bach2 in murine Tfh cells resulted in a rapid loss of their phenotype and subsequent breakdown of the GC response. Low Bach2 expression levels are required to maintain high expression of the signature cytokine IL-21, the coinhibitory receptor TIGITand the transcriptional repressor Bcl-6. In stark contrast to the regulatory network in GC B cells, Bach2 in Tfh cells is not coexpressed with Bcl-6 at high levels to inhibit the antagonizing factor Blimp-1, but suppresses Bcl-6 by direct binding to the promoter. These data reveal that by replacing an activating complex of Batf and Irf-4 at the Bcl-6 promoter, Bach2 regulates the transcriptional network of Tfh cells in a different way, as in GC B cells.