Molecular Mechanism of Long-Term Viability Acquisition of CNS-resident Monocytes Essential for Autoimmune Disease Relapse

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07075
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49070:Immunology-related
• Research Institution: Hokkaido University
• Principal Investigator: Hojyo Shintaro 北海道大学, 遺伝子病制御研究所, 准教授 (90585556)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 多発性硬化症 / 実験的自己免疫性脳脊髄炎 / 骨髄系細胞 / T細胞 / 中枢神経系 / サイトカイン / サイトカイン受容体 / ゲートウェイ反射

Outline of Final Research Achievements

In this study, we aimed at clarifying the molecular mechanism by which myeloid cells migrating from the periphery to the CNS after the initial onset of experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis (MS), acquire long-term viability in the CNS during remission and are involved in pain-dependent neuroinflammatory relapse. We found that myeloid cells of peripheral origin in the CNS in remission constitutively receive survival signals via GM-CSF produced by blood endothelial cells, and are reactivated by pain stimuli, which causes relapse of the disease. Our results suggest that suppression of GM-CSF-mediated signaling may be an effective therapeutic approach in relapsing-remitting inflammatory CNS diseases such as MS.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

本研究は、MSの病態モデルを基盤として我々が独自に発見した痛みゲートウェイ反射機構の詳細を解明する計画であり、自己免疫疾患寛解期における末梢由来CNS骨髄系細胞の長期生存能の獲得についてその分子機序を明らかにすることを目的とした。本研究成果により、(1)これまで知られていない末梢骨髄系細胞とは性状を異にするCNS骨髄系細胞の生活環、(2)自己免疫疾患の病態修飾における免疫系と神経系の相互作用についての新たな理解や概念の確立、(3)自己免疫疾患の再発を抑制しうる新たな臨床的介入法を提示することができた。