The M~5C RNA Methyltransferase Nsun2 Regulates The Differentiation And Function Of CD4 T Cells

Objective:To investigate the regulatory effect of m~5C RNA methyltransferase Nsun2on the differentiation and function of CD4 T cells.Methods:The Nsun2 gene conditional knockout mouse model was established by CRISPR/Cas9 gene editing technology and Cre-Loxp system,and the mouse was used as a research tool to analyze the effect of m~5C methyltransferase Nsun2 on T cell development and homeostasis,and Its regulatory effect on CD4~+T cell differentiation and germinal center.In addition,the association of m~5C methyltransferase Nsun2 with mouse disease models was also explored by establishing B16 F0 melanoma,autoimmune encephalomyelitis and acute enteritis models.Results:It was verified that m~5C RNA methyltransferase Nsun2 was highly expressed in T cells at the m RNA and protein levels.Nsun2 deletion does not affect T cell development and homeostasis.The m~5C methyltransferase Nsun2 inhibits the differentiation of Th1 cells but promotes the differentiation of i Treg cells and Th17cells;in the presence of IL-12,Nsun2 deletion promotes Th1 cells differentiation,and Nsun2 deletion makes i Treg less sensitive to TGF-βsignaling.The m~5C methyltransferase Nsun2 plays a key regulatory function in the promotion of GC responses,and deletion of the m~5C methyltransferase Nsun2 reduces the proportion of Tfh cells and GCB cells.In the mouse B16 F0 melanoma model,m~5C methyltransferase Nsun2 deletion did not affect tumor development;in the EAE model,m~5C methyltransferase Nsun2 deletion caused the mice to be more severe in the EAE pathogenesis model;In the acute enteritis model,there was no significant difference in the body weight of the methyltransferase Nsun2-null mice.Conclusion:The m~5C methyltransferase Nsun2 does not affect T cell development and homeostasis,but it regulates the differentiation of na?ve CD4~+T cells into Th1,Th17 and i Treg cells,and the m~5C methyltransferase Nsun2 promotes GC responses.The m~5C methyltransferase Nsun2 plays an important regulatory role in EAE disease models.