STAT5 promotes accessibility and is required for BATF-mediated plasticity at the Il9 locus.
STAT5 promotes accessibility and is required for BATF-mediated plasticity at the Il9 locus.
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DOI：
10.1038/s41467-020-18648-6
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发表时间：
2020-09-28
影响因子：
16.6
通讯作者：
Kaplan MH
中科院分区：
文献类型：
--
作者：
Fu Y;Wang J;Panangipalli G;Ulrich BJ;Koh B;Xu C;Kharwadkar R;Chu X;Wang Y;Gao H;Wu W;Sun J;Tepper RS;Zhou B;Janga SC;Yang K;Kaplan MH
辅助性T细胞分化需要谱系定义转录因子和在多个亚群之间共享表达的因子。BATF是多种Th亚群发育所必需的，但以谱系特异性方式发挥作用。BATF是Th 9细胞中IL-9产生所需的，但与其作为Th 17细胞中先锋因子的功能相反，BATF对于Il 9基因座的可及性既不充分也不需要。在这里，我们表明，STAT 5是最早的因子结合和重塑的Il 9基因座，以允许BATF结合在小鼠和人的Th 9培养物。在其他Th谱系中观察到STAT 5介导BATF可及性的能力，并允许获得IL-9分泌表型。STAT 5和BATF将Th 17细胞转化为介导过敏性气道炎症和抗肿瘤免疫中的IL-9依赖性作用的细胞。因此，BATF需要STAT 5信号来介导Il 9基因座的可塑性。BATF是T辅助细胞9产生IL-9所需的转录因子。在本文中，作者表明，IL 9位点需要STAT 5才能使BATF以这种方式发挥作用，并且这种相互作用可以将其他T辅助细胞亚群重新编程为IL-9产生细胞，从而调节对疾病的免疫反应。
T helper cell differentiation requires lineage-defining transcription factors and factors that have shared expression among multiple subsets. BATF is required for development of multiple Th subsets but functions in a lineage-specific manner. BATF is required for IL-9 production in Th9 cells but in contrast to its function as a pioneer factor in Th17 cells, BATF is neither sufficient nor required for accessibility at the Il9 locus. Here we show that STAT5 is the earliest factor binding and remodeling the Il9 locus to allow BATF binding in both mouse and human Th9 cultures. The ability of STAT5 to mediate accessibility for BATF is observed in other Th lineages and allows acquisition of the IL-9-secreting phenotype. STAT5 and BATF convert Th17 cells into cells that mediate IL-9-dependent effects in allergic airway inflammation and anti-tumor immunity. Thus, BATF requires the STAT5 signal to mediate plasticity at the Il9 locus. BATF is a transcription factor that is needed for IL-9 production by T helper 9 cells. Here the authors show that STAT5 is needed at the Il9 locus to enable BATF to function in this manner and that this interaction can reprogram other T helper subsets into IL-9 producing cells, thus regulating the immune response to disease.
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影响因子：
16.6
作者：
Koh B;Abdul Qayum A;Srivastava R;Fu Y;Ulrich BJ;Janga SC;Kaplan MH
通讯作者：
Kaplan MH
影响因子：
9
作者：
Kaplan MH
通讯作者：
Kaplan MH
影响因子：
4.4
作者：
Bruns, HA;Schindler, U;Kaplan, MH
通讯作者：
Kaplan, MH
DOI：
10.1073/pnas.162360199
发表时间：
2002-08-06
影响因子：
11.1
作者：
Guo, LY;Hu-Li, J;Paul, WE
通讯作者：
Paul, WE
影响因子：
32.4
作者：
Kaplan, MH;Schindler, U;Grusby, MJ
通讯作者：
Grusby, MJ