2018 Fiscal Year Final Research Report
Functional analyses of leukocyte integrins and its regulatory molecule in glomerulonephritis and those application for cell transfer therapy
| Project/Area Number |
16K09611
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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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| Research Field |
Kidney internal medicine
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| Research Institution | Fujita Health University (2018)
Nagoya University (2016-2017) |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
丸山 彰一 名古屋大学, 医学系研究科, 教授 (10362253)
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| Research Collaborator |
ARASE Hisashi
DU Qiuna
SUGIYAMA Yutaka
KITAGAWA Akimitsu
KOBAYASHI Yoichi
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Keywords | 抗腎糸球体基底膜抗体型腎炎 / 白血球活性化 / 接着因子 / 好中球 / 免疫複合体 |
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| Outline of Final Research Achievements |
【Background】PILRα expressed on leukocytes has regulatory functions in leukocyte β2 integrin activation during acute inflammation. Here, we investigated its roles in antibody-mediated glomerular inflammation.【Results】PILRα-/- mice with NTS-GN demonstrated severe glomerular injury. Enhanced glomerular neutrophil accumulation was observed in NTS-GN PILRα-/- only under pre-immunized conditions. PILRα-/- neutrophils exhibited enhanced spreading and adhesion to ICs compared to those in WT cells.【Conclusion】PILRα negatively regulates antibody-mediated neutrophil recruitment, leading to renal injury, by inhibiting Mac-1 integrin activation.
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| Free Research Field |
腎臓病学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究から白血球発現分子PILRαの接着因子Mac-1制御を介する抗体型糸球体腎炎抑制効果が明らかとなった。またPILRαによる接着因子活性化抑制機能は炎症時にのみ発揮された。したがってPILRαの活性化は、抗体型糸球体腎炎のみならず、関節リウマチ、全身性エリテマトーデスなどの炎症性自己免疫疾患に対する有望な治療ターゲットとして考えられる。
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