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.

Article link：https://www.nature.com/articles/s41467-023-36595-w