Autoimmune neurologic diseases

Oral

Suppression of Regulatory T Cells by Exosomes in Multiple Sclerosis

Friday, June 16
3:15 PM - 3:30 PM

Exosomes are extracellular vesicles which are involved in intercellular communications by delivering a variety of molecules such as miRNAs. MiRNAs are involved in differentiation and function of helper T cells, which play a pivotal pathogenic role in multiple sclerosis (MS). In this study, exosomes were collected from the plasma of patients with MS and healthy controls (MS-exo and HC-exo). We performed comprehensive analysis of exosomal miRNAs in MS, for the first time to our knowledge. The miRNA profiles clearly differentiated MS-exo from HC-exo. RT-qPCR validated four miRNAs that were increased in MS-exo. After co-culture with T cells, MS-exo decreased the frequency of IFNg-IL17A-Foxp3+ Treg cells compared with HC-exo. Among the upregulated miRNAs, the amount of let-7i in the added exosomes was negatively correlated with the frequency of Treg cells in this experiment. Transfection of let-7i reduced the frequency of Treg cells, and further experiments suggested that this was via suppression of insulin-like growth factor 1 receptor (IGF1R) and transforming growth factor-beta receptor 1 (TGFBR1). Knockdown of these receptors were shown to inhibit differentiation of Treg cells. Furthermore, there was reduced expression of these receptors on naive CD4+ T cells in the peripheral blood of MS patients. The frequency of Treg cells in the peripheral blood positively correlated with TGFBR1 expression on naive CD4+ T cells. In summary, this study suggests that exosomes play a pathological role in MS by suppressing Treg cells via let-7i-IGF1R/TGFBR1 axis.

Kimitoshi Kimura

Department of Immunology, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), Japan

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Hirohiko Hohjoh

Department of Molecular Pharmacology, National Institute of Neuroscience, NCNP, Japan

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Masashi Fukuoka

Department of Molecular Pharmacology, National Institute of Neuroscience, NCNP, Japan

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Wakiro Sato

Department of Immunology, National Institute of Neuroscience, NCNP, Japan

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Ryosuke Takahashi

Department of Neurology, Kyoto University Graduate School of Medicine

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Takashi Yamamura

Department of Immunology, National Institute of Neuroscience, NCNP, Japan

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Suppression of Regulatory T Cells by Exosomes in Multiple Sclerosis



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