Elucidation of pathogenesis of intractable asthma by analyzing immunological mechanisms of IL-33 production
| Project/Area Number |
17K08326
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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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| Research Field |
Pharmacology in pharmacy
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| Research Institution | Setsunan University |
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Principal Investigator |
Nabe Takeshi 摂南大学, 薬学部, 教授 (40228078)
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| Co-Investigator(Kenkyū-buntansha) |
松田 将也 摂南大学, 薬学部, 助教 (30783005)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | IL-33 / 喘息 / アトピー / ステロイド / 2型自然リンパ球 / ステロイド抵抗性 / IL－33 / Th2細胞 / ILC2 / IL-5 / インターロイキン-33 / 気管支喘息 / アレルギー / 気道炎症 / マクロファージ / IgG / Fcγ受容体 / B細胞 / 樹状細胞 / 獲得免疫系 / 自然免疫系 / 抗喘息薬 |
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| Outline of Final Research Achievements |
Allergic mechanisms underlying IL-33 production and roles of IL-33 in intractable asthma were analyzed. In antigen-induced IL-33 production in the lung of sensitized mice, mechanisms of incorporation of antigen-IgG antibody complex into alveolar macrophages were involved. On the other hand, in steroid-resistant asthma model that were developed by us as an intractable asthma model, IL-33 production was steroid-sensitive, whereas infiltration of IL-33 receptor-possessing type 2 innate lymphoid cells into the lung was steroid-resistant. Furthermore, expression of IL-33 receptor gene was up-regulated in the lung. In conclusion, IL-33 receptor activation rather than IL-33 production should be involved in the pathogenesis of intractable asthma.
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| Academic Significance and Societal Importance of the Research Achievements |
喘息は吸入ステロイドによってコントロール可能であるとされるが、薬物治療を受けている喘息患者の5-10％はステロイドに抵抗性であるとされる。本研究成果により、ステロイド抵抗性のような難治性喘息の発症には、IL-33の受容体の発現増強を介した機序が存在することが示唆された。したがって、IL-33受容体の遮断や受容体作用後のシグナル伝達を遮断するような薬物が、難治性喘息の治療薬となり得る可能性が考えられた。本研究の成果は、難治性喘息に対する新しい治療薬の開発に資するものである。
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Report
(4 results)
Research Products
(31 results)
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[Journal Article] Antigen-specific airway IL-33 production depends on FcγR-mediated incorporation of the antigen by alveolar macrophages in sensitized mice2018
Author(s)
Takeshi Nabe,Masaya Matsuda, Tomoki Ishida, Nau Tsujimoto, Hitomi Kido, Haruna Kanaya, Hiromu Takahashi, Naoki Takemoto, Miku Nomura, Keiichi Ishihara, Satoshi Akiba, Nobuaki Mizutani
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Journal Title
Immunology
Volume: 155
Issue: 1
Pages: 99-111
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Regulation of allergic airway inflammation by adoptive transfer of CD4+ T cells preferentially producing IL-10.2017
Author(s)
Matsuda M, Doi K, Tsutsumi T, Fujii S, Kishima M, Nishimura K, Kuroda I, Tanahashi Y, Yuasa R, Kinjo T, Kuramoto N, Mizutani N, Nabe T
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Journal Title
Eur J Pharmacol
Volume: 812
Pages: 38-47
DOI
Related Report
Peer Reviewed
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