2021 Fiscal Year Final Research Report

Development of immunotherapy through C-type lectin receptors for chronic wounds

Research Project

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Project/Area Number	19H03812
Research Category	Grant-in-Aid for Scientific Research (B)
Allocation Type	Single-year Grants
Section	一般
Review Section	Basic Section 56070:Plastic and reconstructive surgery-related
Research Institution	Tohoku University
Principal Investigator	TACHI Masahiro 東北大学, 医学系研究科, 名誉教授 (50312004)
Co-Investigator(Kenkyū-buntansha)	川上和義東北大学, 医学系研究科, 教授 (10253973) 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, 非常勤講師 (30569471)
Project Period (FY)	2019-04-01 – 2022-03-31
Keywords	慢性創傷 / 創傷治癒 / 好中球 / C型レクチン受容体
Outline of Final Research Achievements	C-type lectin receptors (CLRs) recognize microbial polysaccharides. The precise roles of these CLRs in wound healing remain unclear. This study was conducted to determine the roles of Dectin-1 and Dectin-2 in wound healing, with a particular focus on the kinetics of neutrophilic inflammatory response. Wounds were created on the backs of C57BL/6 mice, and the effects of Dectin-1 or Dectin-2 deficiency. We also analyzed wound closure, histological findings, and neutrophilic inflammatory response, including neutrophil extracellular trap formation. We found that Dectin-1 contributed to the acceleration of wound healing by inducing early-phase neutrophil accumulation, whereas Dectin-2 was involved in prolonged neutrophilic responses and neutrophil extracellular trap formation, leading to delayed wound healing. These results suggest that Dectin-1 and Dectin-2 have different roles in wound healing through their different effects on the neutrophilic response.
Free Research Field	形成外科学
Academic Significance and Societal Importance of the Research Achievements	褥瘡や糖尿病性下腿潰瘍などの難治性創傷では、好中球性炎症反応が治癒遷延に関与していることが示唆されているが、これまで好中球をターゲットとした治療法は存在しない。今回の解析により、C型レクチン受容体（CLRs）であるDectin-1、Dectin-2が好中球性炎症反応に拮抗的に関与することが明らかになり、CLRsの免疫応答を介した治療法が確立されれば、長年課題とされている好中球性炎症反応を制御することが可能となり、社会的意義は大きい。