Contribution of C-type lectin receptor-mediated signaling to neutrophil extracellular traps in skin ulcers
| Project/Area Number |
18K09473
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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 56070:Plastic and reconstructive surgery-related
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| Research Institution | Tohoku University |
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Principal Investigator |
Akiko Yano 東北大学, 医学系研究科, 非常勤講師 (70612224)
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| Co-Investigator(Kenkyū-buntansha) |
菅野 恵美 東北大学, 医学系研究科, 准教授 (10431595)
丹野 寛大 東北大学, 医学系研究科, 助教 (10755664)
高木 尚之 東北大学, 医学系研究科, 助教 (30569471)
館 正弘 東北大学, 医学系研究科, 教授 (50312004)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 慢性創傷 / 好中球 / ネトーシス / C型レクチン受容体 / Dectin（デクチン）-2 / 糖尿病性足壊疽 / ネトーシス (NETosis) / 感染 |
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| Outline of Final Research Achievements |
C-type lectin receptors recognize microbial polysaccharides. The C-type lectin receptors such as dendritic cell-associated C-type lectin (Dectin)-1 and Dectin-2, which are triggered by β-glucan and α-mannan, respectively, contribute to upregulation of the inflammatory response. This study was conducted to determine the roles of Dectin-1 and Dectin-2 in skin wound healing, with a particular focus on the kinetics of neutrophilic inflammatory response. Full-thickness wounds were created on the backs of C57BL/6 mice, and the effects of Dectin-1 or Dectin-2 deficiency and those of β-glucan or α-mannan administration were examined. We also analyzed wound closure, histological findings, and neutrophilic inflammatory response, including neutrophil extracellular trap formation. We found that Dectin-2 was involved in prolonged neutrophilic responses and neutrophil extracellular trap formation, leading to delayed wound healing.
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| Academic Significance and Societal Importance of the Research Achievements |
糖尿病性足壊疽など慢性創傷は、血流不全(血栓)、感染症に加え、好中球の機能異常が関与する複合的な病態であり、糖尿病患者の25%が生涯に足壊疽を形成することが報告されている。これまで、血流不全、感染症に対する治療法は様々検討されているが、好中球の機能異常に関する研究、治療法は発展途上にあった。
本研究成果により、難治性皮膚潰瘍の治癒遅延に好中球のネトーシスが関与し、さらにその現象にC型レクチン受容体であるDectin-2の関与が明らかになったことから、今後、Dectin-2阻害によるネトーシス制御、皮膚潰瘍治療法への応用が視野に入り、社会的意義は非常に高い。
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Report
(4 results)
Research Products
(8 results)
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[Journal Article] Dectin-2-Mediated Signaling Leads to Delayed Skin Wound Healing through Enhanced Neutrophilic Inflammatory Response and Neutrophil Extracellular Trap Formation.2019
Author(s)
Miura T, Kawakami K, Kanno E, Tanno H, Tada H, Sato N, Masaki A, Yokoyama R, Kawamura K, Kitai Y, Takagi N, Yamaguchi K, Yamaguchi N, Kyo Y, Ishii K, Imai Y, Saijo S, Iwakura Y, Tachi M.
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Journal Title
J Invest Dermatol
Volume: 139(3)
Issue: 3
Pages: 702-711
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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