MiR-30a inhibits Th17 differentiation and demyelination of EAE mice by targeting the IL-21R

- MiR-30a level is decreased during Th17 differentiation and process of MS and EAE.
- Enforced constitutive expression of miR-30a inhibits Th17 differentiation.
- In vivo miR-30a overexpression leads to fewer Th17 generation and alleviative EAE.
- IL-21R is a direct target of miR-30a.

T helper cells 17 (Th17) are recognized as key participants in the pathogenesis of chronic autoimmune diseases such as multiple sclerosis (MS). Regulation of Th17 differentiation is a valuable strategy for diagnosis and treatment of these complicated immune disorders. Here, by genome-wide expression profiling of microRNAs (miRs), we screened miR-30a, whose level was greatly decreased during Th17 differentiation and the process of demyelination disease, both in MS patients and experimental autoimmune encephalomyelitis (EAE) mice. Enforced constitutive expression of miR-30a in naïve T cells inhibited their differentiation into Th17, and in vivo overexpression of miR-30a resulted in fewer Th17 and alleviative EAE. Moreover, target prediction analysis and dual luciferase report assay revealed that interleukin-21 receptor (IL-21R) was a direct target of miR-30a, a finding consistent with the results that miR-30a downregulated the expression of IL-21R, while overexpression of IL-21R alleviated the inhibitory effect of miR-30a on Th17 differentiation. Taken together, our findings imply that miR-30a inhibits Th17 differentiation and the pathogenesis of MS by targeting IL-21R.