Nsun2 Coupling with RoRγt Shapes the Fate of Th17 Cells and Promotes Colitis

Overview

Journal Nat Commun

Specialty Biology

Date 2023 Feb 15

PMID 36792629

Authors

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

Affiliations

Soon will be listed here.

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 (mC) 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 mC formation and consequently enhanced mRNA stability. Our study demonstrates a mC mediated cell intrinsic function in Th17 cells and suggests Nsun2 as a potential therapeutic target for autoimmune disease.

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