STAT5 Represses a STAT3-Independent Th17-like Program during Th9 Cell Differentiation.
STAT5 Represses a STAT3-Independent Th17-like Program during Th9 Cell Differentiation.
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在Th9细胞分化过程中，STAT5抑制stat3独立的th17样程序。
DOI：
10.4049/jimmunol.2100165
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发表时间：
2021-09-01
期刊：
影响因子：
--
通讯作者：
Olson MR
中科院分区：
文献类型：
--
作者：
Canaria DA;Yan B;Clare MG;Zhang Z;Taylor GA;Boone DL;Kazemian M;Olson MR
产生IL-9的T辅助细胞，称为Th 9细胞，有助于对寄生虫和癌症的免疫，但在过敏性疾病和结肠炎中具有有害作用。Th 9细胞响应于IL-4和TGF-β而分化，但这些信号不足以在不存在IL-2的情况下驱动Th 9分化。IL-2诱导的STAT 5激活是Il 9增强子和启动子区域内的染色质可及性所需的，并直接反式激活Il 9基因座。STAT 5还抑制Th 9细胞发育过程中的基因表达，但这些作用不太明确。在这里，我们证明，人类过敏相关的Th 9细胞表现出STAT 5介导的基因抑制的签名，这是与沉默的Th 17样转录签名。在小鼠Th 9细胞分化中，阻断IL-2/STAT 5信号转导诱导IL-17和Th 17相关转录因子Rorγt的表达。然而，IL-2剥夺的Th 9细胞没有表现出显著的Th 17或STAT 3相关的转录特征。与这些观察结果一致，在这些条件下产生IL-17的细胞的分化是STAT 3非依赖性的，但确实需要Rorγt和BATF。此外，Rorγt和BATF的异位表达部分挽救了STAT 3缺陷型Th 17细胞中的IL-17产生，突出了这些因子在此过程中的重要性。虽然在IL-2剥夺的Th 9条件下，产生IL-17的细胞的分化不需要STAT 3，但它们的延长存活是STAT 3依赖性的，这可能解释了为什么在体内通常观察不到不依赖于STAT 3的IL-17产生。总之，我们的数据表明，IL-2/STAT 5信号转导在体外和过敏性疾病中控制Th 9与Th 17样分化程序的平衡中起重要作用。
IL-9-producing T helper cells, termed Th9 cells, contribute to immunity against parasites and cancers but have detrimental roles in allergic disease and colitis. Th9 cells differentiate in response to IL-4 and TGF-β, but these signals are insufficient to drive Th9 differentiation in the absence of IL-2. IL-2-induced STAT5 activation is required for chromatin accessibility within Il9 enhancer and promoter regions and directly transactivates the Il9 locus. STAT5 also suppresses gene expression during Th9 cell development, but these roles are less well defined. Here we demonstrate that human allergy-associated Th9 cells exhibited a signature of STAT5-mediated gene repression that is associated with the silencing of a Th17-like transcriptional signature. In murine Th9 cell differentiation, blockade of IL-2/STAT5 signaling induced the expression of IL-17 and the Th17-associated transcription factors Rorγt. However, IL-2-deprived Th9 cells did not exhibit a significant Th17- or STAT3-associated transcriptional signature. Consistent with these observations, differentiation of IL-17-producing cells under these conditions was STAT3-independent, but did require Rorγt and BATF. Further, ectopic expression of Rorγt and BATF partially rescued IL-17 production in STAT3-deficient Th17 cells, highlighting the importance of these factors in this process. While STAT3 was not required for the differentiation of IL-17-producing cells under IL-2-deprived Th9 conditions, their prolonged survival was STAT3-dependent, potentially explaining why STAT3-independent IL-17 production is not commonly observed in vivo. Together, our data suggest that IL-2/STAT5 signaling plays an important role in controlling the balance of a Th9 vs a Th17-like differentiation program in vitro and in allergic disease.
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影响因子：
16.6
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
通讯作者：
Kaplan MH
影响因子：
32.4
作者：
Guo, Xiaohuan;Qiu, Ju;Tu, Tony;Yang, Xuanming;Deng, Liufu;Anders, Robert A.;Zhou, Liang;Fu, Yang-Xin
通讯作者：
Fu, Yang-Xin
DOI：
10.1084/jem.20080218
发表时间：
2008-07-07
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Ma CS;Chew GY;Simpson N;Priyadarshi A;Wong M;Grimbacher B;Fulcher DA;Tangye SG;Cook MC
通讯作者：
Cook MC
DOI：
10.1073/pnas.1301138111
发表时间：
2014-03-04
影响因子：
11.1
作者：
Liao, Wei;Spolski, Rosanne;Leonard, Warren J.
通讯作者：
Leonard, Warren J.
DOI：
10.4049/jimmunol.1303184
发表时间：
2014-07-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Bassil R;Orent W;Olah M;Kurdi AT;Frangieh M;Buttrick T;Khoury SJ;Elyaman W
通讯作者：
Elyaman W