N 6 -methyladenosine (m 6 A) is the most extensive studied RNA modification across various species, and the important effect of m 6 A modification in immune system has been revealed in distinct contexts, including mRNA metabolism, cell differentiation, proliferation and response to stimulation. Previous studies from Hua-Bing Li group demonstrated that m 6 A methyltransferase METTL3 control T cells homeostasis and sustain the suppressive function of regulatory T cells (Tregs). However, the role of m 6 A methyltransferase in other subtype of T cells remains unknown.
T helper cells 17 (Th17) play a pivotal role in host defense and autoimmunity. In this study, the scientists found that the loss of METTL3 in T cells caused serious defect of Th17 cell differentiation, and impeded the development of experimental autoimmune encephalomyelitis (EAE). They generated Mettl3 f/f Il17a Cre mice and observed that METTL3 deficiency in Th17 cells significantly suppressed the development of EAE and displayed less Th17 cells infiltration into CNS.
m 6 A modification has been reported to participate in RNA metabolism, predominantly affecting RNA stability. SOCS gene mRNAs have been documented as m 6 A targets in CD4 + T cells, and deletion of METTL3 led to attenuation of SOCS mRNA decay. Here, they verified that depletion of METTL3 facilitated SOCS3 RNA stability, then further attenuated IL-17A and CCR5 expression, disrupted Th17 cells differentiation and infiltration, and eventually attenuated the process of EAE.
Collectively, the scientists highlight that m 6 A modification sustains Th17 cell function, which provides new insights into the regulatory network of Th17 cells, and also implies a potential therapeutic target for Th17 cell mediated autoimmune disease.
Science China Life Sciences