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

ABSTRACT: 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 TGFBR

SUBMITTER: Kimura K 

PROVIDER: S-EPMC5750223 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature