Schwann cell derived small extracellular vesicles function as TNFa decoys in peripheral nerve injury

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K22994
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0906:Surgery related to the biological and sensory functions and related fields
• Research Institution: Chiba University
• Principal Investigator: Hirosawa Naoya 千葉大学, 大学院医学研究院, 特任助教 (10882748)
• Project Period (FY): 2020-09-11 – 2022-03-31
• Keywords: シュワン細胞 / エクソソーム / 末梢神経障害性疼痛

Outline of Final Research Achievements

In peripheral nerve injury (PNI), Schwann cells (SCs) serve as first responders and regulate　neuro-inflammation, regeneration, and pain. Tumor necrosis factor alpha (TNFα) is expressed by SCs early in PNI and orchestrates Wallerian degeneration (WD). The spatial and temporal regulation of TNFα is key in PNI. Herein, we demonstrate that SCs release small extracellular vesicles (sEVs) that attenuate TNFα responses. The activity of SC-derived sEVs reflect TNFα receptor (TNFR1), which is abundant in the sEV membrane and serves as a decoy, inhibiting TNFα from binding to SC TNFα receptors that trigger pro-inflammatory responses. SC-derived sEVs attenuate WD and pain induced by TNFα in sciatic nerves and thus, constitute a previously unrecognized, naturally occurring regulatory system in PNI.

Free Research Field

末梢神経

Academic Significance and Societal Importance of the Research Achievements

難治性末梢神経障害は、依然確立された治療がなく、患者さんの肉体的精神的負担のみならず、疼痛の慢性化に伴う医療費の増大に繋がる。我々は今回、末梢神経内でメインの細胞であるシュワン細胞、近年注目を集めている細胞外小胞体、エクソソームに注目し研究を行った。シュワン細胞由来エクソソームは末梢神経障害におけるキーとなるTNFaの抑制を行うことを見出し、より確実に末梢神経障害部位にエクソソームを寄与することを目的とし更なる研究を行う。このエクソソームを活用した末梢神経障害治療が今後大きくこの分野の治療を変えていく可能性を見出した。