Elucidation of the role of ITAM-Card9 pathway in beta c cytokine receptor signaling

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07551
• 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: Kagoshima University
• Principal Investigator: Iizasa Ei'ichi 鹿児島大学, 医歯学域医学系, 助教 (20631998)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: GM-CSF / ITAM / Card9 / FcRγ / DAP12 / 多発性硬化症 / IL-3 / IL-5

Outline of Final Research Achievements

Immunoreceptor tyrosine-based activation motif (ITAM)-bearing moelcules, such as FcRγ and Dap12, have essential roles in immune responses downstream of pattern recognition receptors (PRRs) in macrophages and dendritic cells. It has been well studied that the ITAM-coupled PRRs recognition of pathogens induces phosphorylation of Syk and elicits immune response via Card9. However, the functions of these molecules in cytokine signaling remain unclear. In this study, we show that FcRγ, Syk, and Card9 also play important roles in GM-CSF receptor signaling.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

本研究は、病原体認識のシグナル伝達で不可欠であるITAM分子やCard9が、GM-CSFの情報伝達にも重要な役割を果たしていることを示したものであり、病原体認識とサイトカインのシグナル伝達に重要な共通分子が存在することが明らかになった学術的意義は大きい。また、GM-CSFは、多発性硬化症、関節リウマチ、クローン病などの膠原病の発症や悪化にも重要な役割を持ち、新たなシグナル伝達分子が明らかになったことにより、新しい治療法開発のターゲットにもなりうる。