| Project/Area Number |
20K08811
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 54020:Connective tissue disease and allergy-related
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| Research Institution | Nihon University |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| 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 / 抗IgE自己抗体 / free IgE / オマリズマブ / アトピー性皮膚炎 / hemokinin 1 |
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| Outline of Research at the Start |
慢性特発性蕁麻疹 (CSU) は, 皮膚マスト細胞の脱顆粒と好塩基球および好酸球の病変への集積が特徴である. CSUの病態をASSTの結果および血清IgE値で分けて検討し, 今回ASST陽性を来すマスト細胞活性化機構の解明とその受容体を決定することを第一の目的とする.
第二の目的は, 皮膚マスト細胞が活性化され産生されるメディエーターが引き金となって好塩基球と好酸球の病変への集積を惹起しているものと考え, 症状のあるCSU患者と健常人の血漿中および皮膚角質の脂質メディエーターを網羅的に解析(脂質メタボローム解析)し,遊走因子および活性化制御因子を同定することである.
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| 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.
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| 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.
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