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


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Article Info

DATE

2018-01-02

AUTHORS

Kimitoshi Kimura, Hirohiko Hohjoh, Masashi Fukuoka, Wakiro Sato, Shinji Oki, Chiharu Tomi, Hiromi Yamaguchi, Takayuki Kondo, Ryosuke Takahashi, Takashi Yamamura

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 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. More... »

PAGES

17

References to SciGraph publications

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41467-017-02406-2

    DOI

    http://dx.doi.org/10.1038/s41467-017-02406-2

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1100092808

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/29295981


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