miR-340 Alleviates Psoriasis in Mice through Direct Targeting of IL-17A

Abstract Th17 cell is a well-known lineage of CD4+ effector Th cells that selectively produce IL-17A and play critical roles during the pathogenesis of autoimmune disease. A microRNA (miRNA) is a small noncoding RNA molecule that functions in posttranscriptional regulation of gene expression. Recently, an increasing number of studies have demonstrated that multiple miRNAs are dysregulated in patients with various autoimmune diseases and mediate autoimmune disease pathologic condition at least in part through the regulation of Th17 response. However, among the few miRNAs identified so far that play possible roles in the differentiation of Th17 cells, they all regulate the Th17 response through targeting negative or positive regulators of Th17 differentiation. In the current study, we sought to identify new miRNAs that can directly regulate the expression of IL-17A, the most important cytokine produced by Th17 cells. Our results showed that the 3′ untranslated region of mouse IL-17A can act as a negative regulatory element to downregulate gene expression. Further study revealed that miR-340 can specifically bind to the 3′ untranslated region of mouse IL-17A and downregulate the expression of endogenous IL-17A. More importantly, we demonstrated that treatment with miR-340 alleviates the clinical severity of imiquimod-induced psoriasis in mice through the downregulation of IL-17A. These data indicate that miR-340 may be a useful therapeutic target for the treatment of psoriasis and other IL-17A–mediated autoimmune diseases.