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MicroRNA let-7e is associated with the pathogenesis of experimental autoimmune encephalomyelitis

Guan, H;Fan, D;Mrelashvili, D;Hao, H;Singh, NP;Singh, UP;Nagarkatti, PS;Nagarkatti, M;

MicroRNAs (miRNAs) play important roles in the regulation of immune responses. There is evidence that miRNAs also participate in the pathogenesis of multiple sclerosis (MS), but how the miRNAs regulate the pathogenesis of MS is still under investigation. The identification of new members of the miRNA family associated with the pathogenesis of MS could facilitate early diagnosis and treatment. Here, we show that the level of miRNA let-7e is significantly upregulated in EAE, an animal model of MS using miRNA array and quantitative real-time PCR. The expression of let-7e was mainly in CD4(+) T cells and infiltrated mononuclear cells of CNS, and highly correlated with the development of EAE. We found that let-7e silencing in vivo inhibited encephalitogenic Th1 and Th17 cells and attenuated EAE, with reciprocal increase of Th2 cells; overexpression of let-7e enhanced Th1 and Th17 cells and aggravated EAE. We also identified IL-10 as one of the functional targets of let-7e. Together, we propose that let-7e is a new miRNA involved in the regulation of encephalitogenic T-cell differentiation and the pathogenesis of EAE.