The role of mast cell and monocyte/mecrophage interaction in the regulation of allergic responses

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K15992
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
• Research Institution: Kanazawa University
• Principal Investigator: Nagata Yuka 金沢大学, 薬学系, 助教 (80802016)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: マスト細胞 / 単球 / マクロファージ

Outline of Final Research Achievements

Mast cells exhibit diverse responses to various antigens, and the affinity of IgE and antigen is the initiating factor for these responses. Although some interactions between mast cells and other immune cells have been suggested in response to antigens, information on the interactions between mast cells and monocytes/macrophages remains limited. This study has investigated that IgE/antigen-induced mast cell allergic responses regulate the differentiation of monocytes into macrophages. Mast cells stimulated by low-affinity antigen promoted the secretion of chemokines, leading to the migration of inflammatory monocytes that eventually differentiate into TNF-alpha or IL-1beta producing macrophages. These observations conclusively suggest that the antigen-specific heterogeneous responses of mast cells influence macrophage differentiation and the prolonged duration of allergic inflammation.

Free Research Field

アレルギー・免疫学

Academic Significance and Societal Importance of the Research Achievements

アレルギー疾患の有病率は依然として高く、多様化するアレルゲン（抗原）によって病態の複雑化が懸念されている。本研究により、低親和性抗原刺激を受けたマスト細胞が遅発性にケモカイン分泌を亢進させ、炎症性単球の遊走を促進し、炎症性サイトカイン産生の多いマクロファージへの分化を誘導することが分かった。マスト細胞は即時型炎症を惹起するのみならず、単球・マクロファージを介して遅発型炎症にも関与すると考えられる。この知見を発展させることで、慢性で難治性のアレルギー炎症応答のメカニズムを解明することが期待される。