Nsun2 coupling with RoRγt shapes the fate of Th17 cells and promotes colitis.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 36792629.
- Also identified by DOI 10.1038/s41467-023-36595-w and PMC identifier 9932167.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
T helper 17 (Th17) cells are a subset of CD4<sup>+</sup> 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<sup>5</sup>C) methyltransferase Nsun2 in mouse CD4<sup>+</sup> 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<sup>5</sup>C formation and consequently enhanced mRNA stability. Our study demonstrates a m<sup>5</sup>C mediated cell intrinsic function in Th17 cells and suggests Nsun2 as a potential therapeutic target for autoimmune disease.
Medical subject headings
- Colitis
- Th17 Cells