The transcriptional coactivator TAZ regulates reciprocal differentiation of TH17 cells and Treg cells
The transcriptional coactivator TAZ regulates reciprocal differentiation of TH17 cells and Treg cells
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转录共激活因子 TAZ 调节 T(H)17 细胞和 T-reg 细胞的相互分化
DOI：
10.1038/ni.3748
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发表时间：
2017-07-01
影响因子：
30.5
通讯作者：
Chen, Lanfen
中科院分区：
文献类型：
--
作者：
Geng, Jing;Yu, Shujuan;Chen, Lanfen
免疫抑制调节性T细胞（T-reg细胞）和辅助性T细胞的炎症性T(H)17亚群谱系的不平衡导致自身免疫性和/或炎症性疾病的发展。本研究发现TAZ是Hippo信号TEAD转录因子的辅激活因子，在T(H)17细胞诱导条件下表达，是T(H)17细胞分化和T(H)17细胞介导的炎症性疾病所必需的。TAZ是T(H)17定义转录因子ROR γ T的关键共激活因子。此外，TAZ通过降低组蛋白乙酰转移酶Tip60介导的T-reg细胞主调控因子Foxp3的乙酰化，从而减弱T-reg细胞的发育，该酶靶向Foxp3进行蛋白酶体降解。相反，在t - regg细胞偏斜条件下，TEAD1的表达和转录因子ROR γ t和Foxp3中TAZ的分离促进了t - regg细胞的分化。此外，TAZ缺乏或TEAD1过表达诱导T-reg细胞分化，而编码TAZ的转基因表达或TAZ的激活引导T(H)17细胞分化。我们的研究结果表明，TAZ在调节T-reg细胞和T(H)17细胞的分化中起着关键作用。
An imbalance in the lineages of immunosuppressive regulatory T cells (T-reg cells) and the inflammatory T(H)17 subset of helper T cells leads to the development of autoimmune and/ or inflammatory disease. Here we found that TAZ, a coactivator of TEAD transcription factors of Hippo signaling, was expressed under T(H)17 cell-inducing conditions and was required for T(H)17 differentiation and T(H)17 cell-mediated inflammatory diseases. TAZ was a critical co-activator of the T(H)17-defining transcription factor ROR gamma t. In addition, TAZ attenuated T-reg cell development by decreasing acetylation of the T-reg cell master regulator Foxp3 mediated by the histone acetyltransferase Tip60, which targeted Foxp3 for proteasomal degradation. In contrast, under T-reg cell-skewing conditions, TEAD1 expression and sequestration of TAZ from the transcription factors ROR gamma t and Foxp3 promoted T-reg cell differentiation. Furthermore, deficiency in TAZ or overexpression of TEAD1 induced T-reg cell differentiation, whereas expression of a transgene encoding TAZ or activation of TAZ directed T(H)17 cell differentiation. Our results demonstrate a pivotal role for TAZ in regulating the differentiation of T-reg cells and T(H)17 cells.