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nature portfolio privacy policy advertising pmx-nsun2-c321a-ires-gfp plasmids scientific discussion pure cd4+cd25−cd45rbhi naive social media nol1/nop2/sun domain yun-gui yang generate pmx-nsun2-ires-gfp duplicates-removed bam files reprints peng-yuan yang nsun2cko cd4+cd25−cd45rbhi naive injecting recombinant mouse-il-17a creative research groups open chromatin regions middle kiz-cuhk joint laboratory nsun2-mediated rna methylation immune-mediated inflammatory diseases yong-liang zhao pmx-ires-gfp vector retro-orbital venous sinus t-cell specific cd4-cre cell-mediated intestinal inflammation nature 548 nature 566 nature 472 nature 557 nature 586 nature 534 nature cell-mediated colitis development nsun2 targets il-17a/il-17f 10 μg/ml anti-ifn-γ employed m5c-merip rt-qpcr protein research post-alignment quality assessment c57bl/6j genetic background secretes pro-inflammation cytokines scrna-seq data produced scrna-seq data processing zi-juan gu kaplan–meier survival curve rip-seq data processing k-nearest-neighbor graph nsun2-mediated m5c influences il-7/stat5/socs pathways high-throughput sequencing data

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         headline:Nsun2 coupling with RoRγt shapes the fate of Th17 cells and promotes colitis
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      headline:Nsun2 coupling with RoRγt shapes the fate of Th17 cells and promotes colitis
      description: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. 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 (m5C) methyltransferase Nsun2 in Th17 cells and the promotion of colitis in a murine model.
      datePublished:2023-02-16T00:00:00Z
      dateModified:2023-02-16T00:00:00Z
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         CD4-positive T cells
         Epigenetics in immune cells
         RNA modification
         T-helper 17 cells
         Science
         Humanities and Social Sciences
         multidisciplinary
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