Nsun2 coupling with RoRγt shapes the fate of Th17 cells and promotes colitis.
Nsun2 coupling with RoRγt shapes the fate of Th17 cells and promotes colitis.
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Nsun2 与 RoRγt 耦合决定 Th17 细胞的命运并促进结肠炎
DOI：
10.1038/s41467-023-36595-w
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发表时间：
2023-02-16
影响因子：
16.6
通讯作者：
Yang, Yun-Gui
中科院分区：
文献类型：
--
作者：
Yang, Wen-Lan;Qiu, Weinan;Zhang, Ting;Xu, Kai;Gu, Zi-Juan;Zhou, Yu;Xu, Heng-Ji;Yang, Zhong-Zhou;Shen, Bin;Zhao, Yong-Liang;Zhou, Qi;Yang, Ying;Li, Wei;Yang, Peng-Yuan;Yang, Yun-Gui
T辅助17（Th 17）细胞是参与自身免疫中的炎症反应的CD 4 + T辅助细胞的子集。Th 17细胞分泌Th 17特异性细胞因子，如IL-17 A和IL-17-F，其由主转录因子RoRγt控制。然而，调节Th 17细胞功能的表观遗传机制仍不完全清楚。在这里，我们揭示了小鼠CD 4 + T细胞中RNA 5-甲基胞嘧啶（m5 C）甲基转移酶Nsun 2的缺失特异性抑制Th 17细胞分化，并阐明了Th 17细胞诱导的结肠炎发病机制。从机制上讲，RoRγt可以将Nsun 2募集到其靶标的染色质区域，包括Il 17 a和Il 17 f，导致转录偶联的m5 C形成，从而增强mRNA稳定性。我们的研究证明了在Th 17细胞中m5 C介导的细胞内在功能，并表明Nsun 2作为自身免疫性疾病的潜在治疗靶点。Th 17细胞产生一系列特征性的Th 17型细胞因子，并表达受表观遗传调节支配的转录因子，以参与Th 17程序。在这里，作者暗示了Th 17细胞中的RNA 5-甲基胞嘧啶（m5 C）甲基转移酶Nsun 2和小鼠模型中结肠炎的促进。
T helper 17 (Th17) cells are a subset of CD4+ T helper cells involved in the inflammatory response in autoimmunity. Th17 cells secrete Th17 specific cytokines, such as IL-17A and IL17-F, which are governed by the master transcription factor RoRγt. However, the epigenetic mechanism regulating Th17 cell function is still not fully understood. Here, we reveal that deletion of RNA 5-methylcytosine (m5C) methyltransferase Nsun2 in mouse CD4+ T cells specifically inhibits Th17 cell differentiation and alleviates Th17 cell-induced colitis pathogenesis. Mechanistically, RoRγt can recruit Nsun2 to chromatin regions of their targets, including Il17a and Il17f, leading to the transcription-coupled m5C formation and consequently enhanced mRNA stability. Our study demonstrates a m5C mediated cell intrinsic function in Th17 cells and suggests Nsun2 as a potential therapeutic target for autoimmune disease. Th17 cells produce a range of characteristic Th17 type cytokines and express transcription factors governed by epigenetic regulation to engage the Th17 programme. Here the authors implicate the RNA 5- methylcytosine (m5C) methyltransferase Nsun2 in Th17 cells and the promotion of colitis in a murine model.
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影响因子：
64.5
作者：
Ivanov, Ivaylo I.;McKenzie, Brent S.;Littman, Dan R.
通讯作者：
Littman, Dan R.
DOI：
10.1155/2014/928461
发表时间：
2014
期刊：
ISRN inflammation
影响因子：
--
作者：
Gálvez J
通讯作者：
Gálvez J
DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
1.2
作者：
Chi, Lijun;Delgado-Olguin, Paul
通讯作者：
Delgado-Olguin, Paul
影响因子：
4.9
作者：
Lee SH;Kwon JE;Cho ML
通讯作者：
Cho ML