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Nsun2 coupling with RoRγt shapes the fate of Th17 cells and promotes colitis

by Zhou, Qi , Zhang, Ting , Yang, Wen-Lan , Qiu, Weinan , Xu, Kai , Zhou, Yu , Shen, Bin , Yang, Ying , Yang, Yun-Gui , Li, Wei , Xu, Heng-Ji , Zhao, Yong-Liang , Yang, Zhong-Zhou , Yang, Peng-Yuan , Gu, Zi-Juan

in 13/1 / 13/21 / 13/31 / 13/51 / 49/39 / 49/90 / 49/91 / 631/250/1619/554/1898 / 631/250/1619/554/1898/1273 / 631/250/2502/2170 / 631/337/1645/2570 / 64/60 / 82/58 / 96/109 / Animal models / Animals / Autoimmune diseases / Autoimmunity / CD4 antigen / Cell differentiation / Cell Differentiation - genetics / Chromatin / Colitis / Colitis - genetics / Cytokines / Differentiation (biology) / Epigenetics / Gene Expression Regulation / Helper cells / Humanities and Social Sciences / Inflammation / Inflammatory bowel disease / Inflammatory response / Interleukin 17 / Lymphocytes / Lymphocytes T / Mice / mRNA stability / multidisciplinary / Nuclear Receptor Subfamily 1, Group F, Member 3 - metabolism / Pathogenesis / Science / Science (multidisciplinary) / Th17 Cells / Therapeutic targets / Transcription factors / Transcription Factors - genetics

2023

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2023

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2023

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Journal Article

Nsun2 coupling with RoRγt shapes the fate of Th17 cells and promotes colitis

Zhou, Qi,

Zhang, Ting,

Yang, Wen-Lan,

Qiu, Weinan,

Xu, Kai,

Zhou, Yu,

Shen, Bin,

Yang, Ying,

Yang, Yun-Gui,

Li, Wei,

Xu, Heng-Ji,

Zhao, Yong-Liang,

Yang, Zhong-Zhou,

Yang, Peng-Yuan,

Gu, Zi-Juan

2023

Overview

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 (m 5 C) 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 m 5 C formation and consequently enhanced mRNA stability. Our study demonstrates a m 5 C 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 (m 5 C) methyltransferase Nsun2 in Th17 cells and the promotion of colitis in a murine model.

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Publisher

Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio

Subject

13/1

/ 13/21

/ 13/31

/ 13/51

/ 49/39

/ 49/90

/ 49/91