Elucidation of mastcell/basophil activation mechanism in chronic spontaneous urticaria

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08811
• 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: Nihon University
• Principal Investigator: OKAYAMA Yoshimichi 日本大学, 医学部, 准教授 (80292605)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: マスト細胞 / IgE / 慢性特発性蕁麻疹 / 好塩基球 / 脂質メディエーター / MRGPRX2 / hemokinin-1 / substance P

Outline of Final Research Achievements

We have previously reported the hyper-expression of Mas-related G protein-coupled receptor X2 (MRGPRX2), which is a receptor for substance P (SP) on skin mast cells (MCs) of patients with severe chronic spontaneous urticaria (CSU). We found that hemokinin-1 (HK-1) was a ligand of MRGPRX2, but high concentration of HK-1 was required for the activation of MCs and HK-1 induced desensitization of MCs. The concentrations of HK-1 in sera from patients with CSU were significantly lower than those from healthy controls. Therefore, HK-1 may inhibit MC activation by SP in healthy controls.
Lipid profiling in sera from CSU patients and healthy controls was performed using liquid chromatography-tandem mass spectrometry/mass spectrometry. The concentrations of 5-hydroxyeicosatetraenoic acid (HETE) in CSU patients were significantly higher than those from healthy controls. 5-HETE induced priming of IgE-dependent basophils degranulation. Thus, 5-HETE would be a new therapeutic target for CSU.

Free Research Field

アレルギー学

Academic Significance and Societal Importance of the Research Achievements

慢性特発性蕁麻疹 (CSU) 患者の皮膚マスト細胞 (MC)の活性化機序としてIgE依存性の機序のみならずMas-related G protein-coupled receptor X2 (MRGPRX2)を介した系が存在し, CSU患者血清中substance P濃度は健常人と比較して有意に高いが, 健常人の皮膚MCもMRGPRX2を発現していることから何らかのMRGPRX2によるMC活性化抑制機構が存在していると考えられた. hemokinin-1がその役割を果たしていることが示唆された. CSU患者の血漿中のアラキドン酸代謝物の5-HETEはCSUの新たな治療標的になる.