The m⁶A modification of Il17a in CD4⁺ T cells promotes inflammation in psoriasis

Psoriasis is a chronic inflammatory skin disorder. The mechanism of psoriasis pathogenesis is not entirely clear. Here, we reported that the level of the N6-methyladenosine (m(6)A) modification was increased in psoriatic CD4(+) T cells compared with healthy controls. In the psoriasis mouse model, depletion of the RNA demethylase, Alkbh5, from CD4(+) T cells promoted the psoriasis-like phenotype and inflammation. Intriguingly, this phenotype and inflammation were alleviated by the ablation of the m(6)A methyltransferase Mettl3 in CD4(+) T cells. Mechanistically, we found that the m(6)A modification of IL17A mRNA increased the expression of IL-17A (an important pro-inflammatory factor in psoriasis) and promoted psoriasis. Thus, our study provided evidence that the m(6)A modification of IL17A in CD4(+) T cells regulates inflammation in psoriasis.