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.

T 辅助细胞 17 (Th17) 细胞是 CD4 ⁺ T 辅助细胞的一个子集，参与自身免疫的炎症反应。Th17 细胞分泌 Th17 特异性细胞因子，如 IL-17A 和 IL17-F，这些细胞因子受主转录因子 RoRγt 控制。然而，调节Th17细胞功能的表观遗传机制仍未完全明了。在这里，我们发现小鼠 CD4 ⁺ T 细胞中RNA 5-甲基胞嘧啶 (m ⁵ C) 甲基转移酶 Nsun2 的缺失特异性抑制 Th17 细胞分化并减轻 Th17 细胞诱导的结肠炎发病机制。从机制上讲，RoRγt 可以将 Nsun2 招募到其目标的染色质区域，包括Il17a和Il17f，从而导致转录偶联的 m ⁵C的形成，从而增强了mRNA的稳定性。我们的研究证明了Th17 细胞中am ^{5 C 介导的细胞内在功能，并表明 Nsun2 作为自身免疫性疾病的潜在治疗靶点。}