Report METTL3-mediated M6a Methylation Orchestrates Mrna Stability and Dsrna Contents to Equilibrate Y8 T1 and Y8 T17 Cells

y8 T cells make key contributions to tissue physiology and immunosurveillance through two main function-ally distinct subsets, y8 T1 and y8 T17. m6A methylation plays critical roles in controlling numerous as-pects of mRNA metabolism that govern mRNA turnover, gene expression, and cellular functional special-ization; however, its role in y8 T cells remains less well understood. Here, we find that m6A methylation controls the functional specification of y8 T17 vs. y8 T1 cells. Mechanistically, m6A methylation prevents the formation of endogenous double-stranded RNAs and promotes the degradation of Stat1 transcripts, which converge to prevent over-activation of STAT1 signaling and ensuing inhibition of y8 T17. Deleting Mettl3, the key enzyme in the m6A methyltransferases complex, in y8 T cells reduces interleukin-17 (IL-17) production and ameliorates y8 T17-mediated psoriasis. In summary, our work shows that METTL3-mediated m6A methylation orchestrates mRNA stability and double-stranded RNA (dsRNA) con-tents to equilibrate y8 T1 and y8 T17 cells.