Regulatory mechanism of innate lymphoid cells by TNFRSF co-stimulatory molecules

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07546
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49070:Immunology-related
• Research Institution: Tohoku University
• Principal Investigator: Okuyama Yuko 東北大学, 医学系研究科, 助教 (50624475)
• Co-Investigator(Kenkyū-buntansha): 河部 剛史 東北大学, 医学系研究科, 准教授 (50834652)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 自然リンパ球 / ILC2 / 補助刺激 / GITR / アレルギー

Outline of Final Research Achievements

We have previously shown that GITR, a TNF receptor-type T cell co-stimulator, promotes proliferation and activation of lung tissue type 2 innate lymphocytes (ILC2) and contributes to the pathogenesis of allergic lung inflammatory disease. In this study, we found that GITR ligand (GITRL) expression is induced by ILC2 itself during inflammation, and ILC2-dependent lung inflammatory disease pathology was attenuated in GITR-L-deficient mice. In addition, the expression changes and functions of each co-stimulatory signal were confirmed in human peripheral blood-derived ILC2. These findings suggest that co-stimulatory signals on ILC2 cells may be involved in the regulation of ILC2 interactions as well as in the regulation of T cell function.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

これまで補助刺激分子はT細胞に発現し、抗原依存的なT細胞の活性化を制御することが知られているが、抗原受容体を持たない自然リンパ球に発現する補助刺激分子はT細胞とは異なる新規の機能を有する。この機能の詳細を解析した点で本研究は学術的な意義が高い。またILC2はアレルギー疾患の発症に関与することから、GITR-GITRLシグナルを介したILC2の機能制御を明らかにすることで、これらを標的としたアレルギー疾患の新規治療法開発に繋がることから、社会的意義が大きい研究成果である。