Analysis of function of STAP-1 for mast cell activation and pathogenesis of bronchial asthma

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08451
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54020:Connective tissue disease and allergy-related
• Research Institution: Hokkaido University of Science (2022-2023); Hokkaido University (2021)
• Principal Investigator: KASHIWAKURA JUNICHI 北海道科学大学, 薬学部, 教授 (90373290)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: STAP-1 / マスト細胞 / IgE / サイトカイン / アレルギー炎症

Outline of Final Research Achievements

Mast cell (MC) expresses FcεRI on the surface and is crutial for acute allergic reaction like anaphylaxis. Upon stimulation via FcεRI, MC is activated and MC activaton events such as degranulation and cytokine production are initiated. Not only kinases, but adaptor proteins are required for the activation as a scaffold protein function. It has been reported that signal-transducing adaptor protein-1 (STAP-1) is involved in TCR-mediated T cell function as a positive regulator. However, it is unknown the functional role of STAP-1 for FcεRI-mediated MC activation. Therefore, it was sought to investigate the function of STAP-1 for IgE-dependent MC activation. It was found that STAP-1 deficiency resulted in increased cytokine producrion, but not degranulation, in activated MC. Also, the deficiency caused dysregulation of STAP-1-dependent interaction of SHP-1 with Lyn after activation. Therefor, STAP-1 is a negative regulatory adaptor protein in MC after IgE-dependent activation.

Free Research Field

免疫学・アレルギー学

Academic Significance and Societal Importance of the Research Achievements

本研究は、STAP-1の発現もしくは機能異常が、マスト細胞による生体恒常性崩壊を導き、アレルギーや自己免疫疾患など、マスト細胞依存性の免疫過剰反応が関わる病気の発症原因の一つになる可能性を示している。そのため、STAP-1の一塩基多型の調査を他の関連遺伝子の一塩基多型と組み合わせることや、マスト細胞内STAP-1発現調節機能の詳細解明は、新規アレルギー治療薬や治療戦略開発につながる可能性があり、国民生活で問題となっているアレルギー疾患の改革が期待できる。