2023 Fiscal Year Final Research Report
Analysis of mediators involved in T cell dependent late asthmatic response
| Project/Area Number |
21K08486
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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 | Clinical Research Center for Allergy and Rheumatology, National Hospital Organization, Sagamihara National Hospital |
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Principal Investigator |
MORI AKIO 独立行政法人国立病院機構(相模原病院臨床研究センター), 先端技術開発研究部, 部長 (80251247)
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| Co-Investigator(Kenkyū-buntansha) |
神山 智 独立行政法人国立病院機構(相模原病院臨床研究センター), 先端技術開発研究部, 研究員 (20626783)
神沼 修 広島大学, 原爆放射線医科学研究所, 教授 (80342921)
大友 隆之 東京薬科大学, 薬学部, 講師 (90463108)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | 気管支喘息 / T 細胞 / 遅発型喘息反応 / メディエータ |
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| Outline of Final Research Achievements |
Mite-specific T cell clones were established from patients who exhibited late asthmatic responses in response to mite allergen challenge. T cell clones were established from ovalbumin (OVA)-specific T cell receptor transgenic mice. Cultured human or mouse bronchial smooth muscle cells were encapsulated in a collagen gel and incubated for 6 days before assaying for contractile activity of T cell supernatants. Several T cell clones produced bronchial smooth muscle contractile activity upon activation. Supernatants were biochemically fractionated by gel filtration and ion exchange. Gene expression and proteomic analysis were performed among clones to search for candidate molecules. Multiple candidate molecules were selected, recombinant proteins were created, and inhibition experiments were conducted using neutralizing antibodies. A candidate molecule showed significant contractile activity, but activities of T cell clone supernatants were not abolished by the neutralizing antibody.
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| Free Research Field |
アレルギー学
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| Academic Significance and Societal Importance of the Research Achievements |
気管支喘息は、IgE抗体を特徴とするアトピー型とIgE抗体の認められない非アトピー型とに分類される。アトピー型のメカニズムは石坂公成先生が発見したIgE抗体による即時型アレルギー反応により説明されたものの、非アトピー型のメカニズムは未解明のままである。われわれの研究によって、T細胞依存性、IgE抗体非依存性の気管支平滑筋収縮（喘息）反応が個体レベル、細胞レベルで証明された。分子レベルで気管支平滑筋収縮メディエータを同定することによって、成人喘息、難治性喘息の半数を占める非アトピー型喘息のメカニズムが解明されるとともに、新規治療法の開発が進むことが期待される。
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