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

Kimitoshi Kimura, Hirohiko Hohjoh, Masashi Fukuoka, Wakiro Sato, Shinji Oki, Chiharu Tomi, Hiromi Yamaguchi, Takayuki Kondo, Ryosuke Takahashi and Takashi Yamamura ()
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Kimitoshi Kimura: National Center of Neurology and Psychiatry
Hirohiko Hohjoh: National Center of Neurology and Psychiatry
Masashi Fukuoka: National Center of Neurology and Psychiatry
Wakiro Sato: National Center of Neurology and Psychiatry
Shinji Oki: National Center of Neurology and Psychiatry
Chiharu Tomi: National Center of Neurology and Psychiatry
Hiromi Yamaguchi: National Center of Neurology and Psychiatry
Takayuki Kondo: Kyoto University Graduate School of Medicine
Ryosuke Takahashi: Kyoto University Graduate School of Medicine
Takashi Yamamura: National Center of Neurology and Psychiatry

Nature Communications, 2018, vol. 9, issue 1, 1-14

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-017-02406-2

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