2020 Fiscal Year Final Research Report

Contribution of invariant natural killer T cells and IFN-gamma to neutrophilic inflammation in skin wounds

Research Project

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Project/Area Number	19K22649
Research Category	Grant-in-Aid for Challenging Research (Exploratory)
Allocation Type	Multi-year Fund
Review Section	Medium-sized Section 55:Surgery of the organs maintaining homeostasis and related fields
Research Institution	Tohoku University
Principal Investigator	Kanno Emi 東北大学, 医学系研究科, 准教授 (10431595)
Co-Investigator(Kenkyū-buntansha)	丹野寛大東北大学, 医学系研究科, 助教 (10755664) 館正弘東北大学, 医学系研究科, 教授 (50312004) 高木尚之東北大学, 医学系研究科, 助教 (30569471) 笠松純東北大学, 医学系研究科, 講師 (60567345) 佐藤光東北大学, 医学系研究科, 助教 (20832124) 丸山良子東北大学, 医学系研究科, 名誉教授 (10275498)
Project Period (FY)	2019-06-28 – 2021-03-31
Keywords	NKT細胞 / 創傷治癒 / 肝臓 / IFN-γ
Outline of Final Research Achievements	Interferon (IFN)-γ is mainly secreted by CD4+ T helper 1 (Th1), natural killer (NK) and NKT cells after skin injury. Although IFN-γ is well known regarding its inhibitory effects on collagen synthesis by fibroblasts in vitro,information is limited regarding its role in wound healing in vivo.In the present study, we analyzed how the defect of IFN-γ affects wound healing. Full-thickness wounds were created on the backs of wild type (WT) C57BL/6 and IFN-γ-deficient (KO) mice. We analyzed the percent wound closure, accumulation of leukocytes, and matrix metalloproteinases (MMPs). IFN-γKO mice exhibited significant attenuation in wound closure on Day 10, characteristics that are associated with prolonged neutrophil accumulation. Expression levels of MMP-2 mRNA were significantly greater in IFN-γKO than in WT. Moreover, under neutropenic conditions created with anti-Gr-1 monoclonal antibodies, wound closure in IFN-γKO mice was recovered through low MMP-2 expression levels.
Free Research Field	基礎看護学
Academic Significance and Societal Importance of the Research Achievements	長年、皮膚に生じる創傷（キズ）は皮膚に存在する線維芽細胞や受傷後創部に遊走する免疫細胞が治すと考えられてきたが、肝臓をはじめとする全身の臓器の関与については不明であった。本研究成果により、肝臓の直接的な関与は解明できなかったが、肝臓に豊富に存在するNKT細胞が主に産生するサイトカインであるインターフェロンγが、創部の好中球性炎症反応、MMP-2産生を制御し、慢性化に関わっていることが明らかになった。今後、MMP-2阻害による新規の慢性創傷治療法の開発に向けての基礎的データを得ることができ、社会的意義は非常に高い。