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

Author

Listed:
  • Kimitoshi Kimura

    (National Center of Neurology and Psychiatry
    Kyoto University Graduate School of Medicine)

  • Hirohiko Hohjoh

    (National Center of Neurology and Psychiatry)

  • Masashi Fukuoka

    (National Center of Neurology and Psychiatry)

  • Wakiro Sato

    (National Center of Neurology and Psychiatry
    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
    Kansai Medical University Medical Center)

  • Ryosuke Takahashi

    (Kyoto University Graduate School of Medicine)

  • Takashi Yamamura

    (National Center of Neurology and Psychiatry
    National Center of Neurology and Psychiatry)

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.

Suggested Citation

  • Kimitoshi Kimura & Hirohiko Hohjoh & Masashi Fukuoka & Wakiro Sato & Shinji Oki & Chiharu Tomi & Hiromi Yamaguchi & Takayuki Kondo & Ryosuke Takahashi & Takashi Yamamura, 2018. "Circulating exosomes suppress the induction of regulatory T cells via let-7i in multiple sclerosis," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-017-02406-2
    DOI: 10.1038/s41467-017-02406-2
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