| Project/Area Number |
19K08895
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 54020:Connective tissue disease and allergy-related
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| Research Institution | St. Marianna University School of Medicine (2022)
Nippon Medical School (2019-2021) |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | 細胞遊走 / 補体 / 関節炎 / 補体受容体 / ケモカイン / ケモカイン受容体 / Arthritis / Complement / Transcytosis / Chemokine / 自己免疫疾患 / 好中球 / 生体イメージング |
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| Outline of Research at the Start |
慢性炎症性疾患において組織で生成されたChemoattractant分子がどのように血液中を循環する免疫細胞を炎症局所へ遊走させるか、その機序は未だ不明である。本研究では、免疫細胞の動態とChemoattractant分子の相互間作用を明らかにする。さらに、炎症下で免疫細胞の遊走を効果的に抑制する標的を同定し、新たな免疫治療法の基礎を確立する。
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| 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.
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| 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。
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