Role of Allergin-1 ligand in the food anaphylaxis model

2023 Fiscal Year Final Research Report

• Project/Area Number: 21H02709
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 49030:Experimental pathology-related
• Research Institution: University of Tsukuba
• Principal Investigator: Tahara Satoko 筑波大学, 生存ダイナミクス研究センター, 講師 (20360589)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 食物アレルギー / 好塩基球 / Allergin-1リガンド

Outline of Final Research Achievements

Mast cells play a central role in type 1 allergic reactions mediated by allergen-IgE-bound FcεRI signaling. Allergy inhibitory receptor 1 (Allergin-1) inhibits FcεRI-mediated signaling in mast cells and plays a vital role in suppressing systemic and cutaneous anaphylaxis and allergic airway hyperresponsiveness, but the ligand for Allergin-1 has not yet been identified. Here, we found that a putative ligand for Allergin-1 was expressed on extracellular vesicles isolated from bone-marrow-derived dendritic cells. We identified Annexin A5 as a functional ligand for Allergin-1 by biochemical and mass-spectrometry analyses. Annexin A5 bound to human and mouse Allergin-1 and suppressed IgE-dependent degranulation from mast cells. Local Annexin A5 administration to the ear skin ameliorated passive cutaneous anaphylaxis in wild-type, but not Allergin-1-deficient, mice. Thus, Annexin A5 is a functional ligand for Allergin-1 that ameliorates type I hypersensitivity.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

Ｉ型アレルギーは、IgE抗体依存的に脱顆粒反応するエフェクター相から惹起されることから、ヒト化抗IgE抗体（Omalizumab）が開発された。しかし、OmalizumabはFcεRIに結合していないフリーのIgEに結合し、FcεRIに結合しているIgEには結合しない。Annexin A5は、IgEで感作されたマスト細胞の脱顆粒反応をAllergin-1依存的に抑制した。このことから、Annexin A5がAllergin-1を介してＩ型アレルギー疾患の新しい治療法の開発に貢献できる可能性がある。