Elucidation of the T cell receptor signaling pathway that determines the functions of gdT cells

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K19102
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Experimental pathology
• Research Institution: The University of Tokyo
• Principal Investigator: Muro Ryunosuke 東京大学, 大学院医学系研究科(医学部), 特任研究員 (80761262)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 胸腺 / T細胞受容体 / γδT細胞 / Syk

Outline of Final Research Achievements

IL-17 producing γδT (γδT17) cells play an important role in the early response to infection, whereas they are involved in the pathogenesis of inflammatory diseases and metastasis. Although the γδT17 cells are known to develop in the thymus, its precise molecular mechanism remained unclear. In this study, we aimed to clarify the molecular mechanism how T cell receptor (TCR) signal controls the development of γδT17 cells in the thymus. Studies with genetically modified mice revealed that Syk functions as a dominant tyrosine kinase in γδTCR signaling. We also found that Syk activates the PI3K/AKT pathway and LAT/ERK pathway, both of which are mandatory for the development of γδT17 cells.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

本研究にて、研究代表者らはγδT細胞におけるSyk依存的なTCRシグナルを同定した。これまでγδT細胞のシグナル伝達機構は典型的αβT細胞と類似していると考えられてきたが、研究代表者らはγδT細胞に特有のTCRシグナル伝達がγδT細胞の機能決定に重要であることを明らかにし、世界に先駆けて発表した。免疫学領域における新たな知見を提供し、学術的意義の高い成果となった。本研究成果から、SykやPI3Kを標的とすることで、炎症性γδT細胞を人為的に制御できる可能性があり、炎症性疾患の治療法確立に繋がる可能性がある。