Nsun2 coupling with RoRγt shapes the fate of Th17 cells and promotes colitis
Wen-Lan Yang, Weinan Qiu, Ting Zhang, Kai Xu, Zi-Juan Gu, Yu Zhou, Heng-Ji Xu, Zhong-Zhou Yang, Bin Shen, Yong-Liang Zhao, Qi Zhou, Ying Yang, Wei Li, Peng-Yuan Yang & Yun-Gui Yang
Abstract
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.
附件下载：
Nsun2 coupling with RoRγt shapes the fate of Th17 cells and promotes colitis, Nat Commun, 16 Feb 2023
Nature Communications, 16 February, 2023, DOI：https://doi.org/10.1038/s41467-023-36595-w
Nsun2 coupling with RoRγt shapes the fate of Th17 cells and promotes colitis
Wen-Lan Yang, Weinan Qiu, Ting Zhang, Kai Xu, Zi-Juan Gu, Yu Zhou, Heng-Ji Xu, Zhong-Zhou Yang, Bin Shen, Yong-Liang Zhao, Qi Zhou, Ying Yang, Wei Li, Peng-Yuan Yang & Yun-Gui Yang
Abstract
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.
文章链接：https://www.nature.com/articles/s41467-023-36595-w