Pathogenic Role of Atypical Chemoattractant Receptors in Immune Complex-induced Arthritis

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K08895
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54020:Connective tissue disease and allergy-related
• Research Institution: St. Marianna University School of Medicine (2022); Nippon Medical School (2019-2021)
• Principal Investigator: Miyabe Yoshishige 聖マリアンナ医科大学, 医学部, 教授 (70632313)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 細胞遊走 / 補体 / 関節炎

Outline of Final Research Achievements

Chemoattractant-induced arrest of circulating leukocytes and their subsequent diapedesis is a fundamental　component of inflammation. However, how tissue-derived chemoattractants are transported into the blood　vessel lumen to induce leukocyte entry into tissue is not well understood. Our in vivo imaging joints has demonstrated that the atypical complement C5a receptor 2 (C5aR2) expressed on endothelial cells were required for the transport of C5a into the vessel lumen in a murine model of immune complex induced arthritis. Transported C5a was required to initiate C5aR1-mediated neutrophil arrest, igniting joint inflammation. Our findings provide new insights into how atypical chemoattractant receptors collaborate with classical signaling chemoattractant receptors to control distinct steps in the recruitment of neutrophils into tissue sites of inflammation.

Free Research Field

膠原病内科学

Academic Significance and Societal Importance of the Research Achievements

現在、補体は血管炎の重要な治療標的であるが、生体内における機能は不明な点が多い。本研究成果は、炎症病態における生体内での補体受容体C5aR2が補体成分C5a輸送に関与し炎症惹起に関与しているという新しい機能を発見し、関節リウマチにおける新しい治療標的となりうる事を示唆している。