2020 Fiscal Year Final Research Report

Contribution of C-type lectin receptor-mediated signaling to neutrophil extracellular traps in skin ulcers

Research Project

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Project/Area Number	18K09473
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 56070:Plastic and reconstructive surgery-related
Research Institution	Tohoku University
Principal Investigator	Akiko Yano 東北大学, 医学系研究科, 非常勤講師 (70612224)
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)
Project Period (FY)	2018-04-01 – 2021-03-31
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
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.
Free Research Field	形成外科学
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。