Circulating exosomes suppress the induction of regulatory T cells via let-7i in multiple sclerosis

Multiple sclerosis (MS) is a T cell-mediated autoimmune disease of the central nervous system. Foxp3 + regulatory T (Treg) cells are reduced in frequency and dysfunctional in patients with MS, but the underlying mechanisms of this deficiency are unclear. Here, we show that induction of human IFN-γ − IL-17A − Foxp3 + CD4 + T cells is inhibited in the presence of circulating exosomes from patients with MS. The exosomal miRNA profile of patients with MS differs from that of healthy controls, and let-7i , which is markedly increased in patients with MS, suppresses induction of Treg cells by targeting insulin like growth factor 1 receptor ( IGF1R ) and transforming growth factor beta receptor 1 ( TGFBR1 ). Consistently, the expression of IGF1R and TGFBR1 on circulating naive CD4 + T cells is reduced in patients with MS. Thus, our study shows that exosomal let-7i regulates MS pathogenesis by blocking the IGF1R/TGFBR1 pathway.