| First Author | Xiao Z | Year | 2023 |
| Journal | Cell Rep | Volume | 42 |
| Issue | 7 | Pages | 112684 |
| PubMed ID | 37355989 | Mgi Jnum | J:337913 |
| Mgi Id | MGI:7508955 | Doi | 10.1016/j.celrep.2023.112684 |
| Citation | Xiao Z, et al. (2023) METTL3-mediated m6A methylation orchestrates mRNA stability and dsRNA contents to equilibrate gammadelta T1 and gammadelta T17 cells. Cell Rep 42(7):112684 |
| abstractText | gammadelta T cells make key contributions to tissue physiology and immunosurveillance through two main functionally distinct subsets, gammadelta T1 and gammadelta T17. m6A methylation plays critical roles in controlling numerous aspects of mRNA metabolism that govern mRNA turnover, gene expression, and cellular functional specialization; however, its role in gammadelta T cells remains less well understood. Here, we find that m6A methylation controls the functional specification of gammadelta T17 vs. gammadelta 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 gammadelta T17. Deleting Mettl3, the key enzyme in the m6A methyltransferases complex, in gammadelta T cells reduces interleukin-17 (IL-17) production and ameliorates gammadelta T17-mediated psoriasis. In summary, our work shows that METTL3-mediated m6A methylation orchestrates mRNA stability and double-stranded RNA (dsRNA) contents to equilibrate gammadelta T1 and gammadelta T17 cells. |
