The transcription factor KLF2 restrains CD4⁺ T follicular helper cell differentiation.
The transcription factor KLF2 restrains CD4⁺ T follicular helper cell differentiation.
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DOI：
10.1016/j.immuni.2015.01.013
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发表时间：
2015-02-17
期刊：
影响因子：
32.4
通讯作者：
Jameson, Stephen C.
中科院分区：
文献类型：
--
作者：
Lee, June-Yong;Skon, Cara N.;Lee, You Jeong;Oh, Soohwan;Taylor, Justin J.;Malhotra, Deepali;Jenkins, Marc K.;Rosenfeld, M. Geoffrey;Hogquist, Kristin A.;Jameson, Stephen C.
T滤泡辅助细胞（Tfh）对于有效的B细胞应答至关重要，然而调节CD4+ T细胞亚群分化的因素尚不完全清楚。这里我们发现KLF2转录因子可以抑制Tfh细胞的产生。激活CD4+ T细胞诱导KLF2缺失导致Tfh细胞生成和B细胞启动增加，而KLF2过表达阻止Tfh细胞生成。KLF2促进转运受体S1PR1的表达，而S1PR1的下调对于高效的Tfh细胞产生至关重要。然而，KLF2还诱导转录因子Blimp-1的表达，抑制转录因子Bcl-6，从而阻碍Tfh细胞分化。此外，KLF2诱导转录因子T-bet和GATA3的表达，并增强Th1的分化。因此，我们的数据表明，KLF2在协调CD4+ T细胞分化中是关键的，它通过两种不同的互补机制：通过控制T细胞定位，以及通过调节定义谱系的转录因子。
T follicular helper (Tfh) cells are essential for efficient B cell responses, yet the factors that regulate differentiation of this CD4+ T cell subset are incompletely understood. Here we found that the KLF2 transcription factor serves to restrain Tfh cell generation. Induced KLF2 deficiency in activated CD4+ T cells led to increased Tfh cell generation and B cell priming, while KLF2 overexpression prevented Tfh cell production. KLF2 promotes expression of the trafficking receptor S1PR1, and S1PR1 downregulation is essential for efficient Tfh cell production. However, KLF2 also induced expression of the transcription factor Blimp-1, which repressed transcription factor Bcl-6 and thereby impaired Tfh cell differentiation. Furthermore, KLF2 induced expression of the transcription factors T-bet and GATA3 and enhanced Th1 differentiation. Hence, our data indicate KLF2 is pivotal for coordinating CD4+ T cell differentiation through two distinct and complementary mechanisms: via control of T cell localization, and by regulation of lineage-defining transcription factors.
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32.4
作者：
Choi YS;Kageyama R;Eto D;Escobar TC;Johnston RJ;Monticelli L;Lao C;Crotty S
通讯作者：
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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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