2017 Fiscal Year Final Research Report
Intracellular function of Sema4A in dendritic cells.
| Project/Area Number |
15K08423
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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 |
Experimental pathology
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| Research Institution | Osaka University |
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Principal Investigator |
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| Co-Investigator(Renkei-kenkyūsha) |
KUMANOGOH Atsushi 大阪大学, 大学院医学系研究科, 教授 (10294125)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Keywords | 自己免疫性疾患 / ANCA関連血管炎 / 免疫セマフォリン |
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| Outline of Final Research Achievements |
Since an interesting association between SEMA4D and antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) was found, we studied the significance of SEMA4D in the pathogenesis of AAV. Serum levels of soluble SEMA4D were elevated in patients with AAV and correlated with disease activity scores. Cell-surface expression of SEMA4D was downregulated in neutrophils from patients with AAV, a consequence of proteolytic cleavage of membrane SEMA4D. Membranous SEMA4D on neutrophils bound to plexin B2 on endothelial cells, and this interaction decreased NET formation. Recombinant plexin B2 successfully inhibited pathogen-induced or ANCA-induced oxidative burst and NET formation.
Thus, neutrophil surface SEMA4D functions as a negative regulator of neutrophil activation. Proteolytic cleavage of SEMA4D as observed in patients with AAV may amplify neutrophil-mediated inflammatory responses. SEMA4D is a promising biomarker and potential therapeutic target for AAV.
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| Free Research Field |
病理学、免疫学
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