2023 Fiscal Year Final Research Report
Adaptation of therapeutic agents for Th1 cell dependent severe asthma using asthmatic murine model
| Project/Area Number |
20K17436
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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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 |
Kouyama SatoshiSatoshi 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)
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| Project Period (FY) |
2020-04-01 – 2024-03-31
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| Keywords | T細胞 / 気管支喘息 / アレルギー反応 |
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| Outline of Final Research Achievements |
Drug candidates were selected from known investigational and approved molecular targeted drugs. Inhibition of activity was observed in T-cell clones that induce late asthmatic response and in T-cell clones that induce eosinophilic inflammation. These were found to have additive inhibitory effects with glucocorticoids. As a cellular diagnosis in animal models, Th2 eosinophil infiltration in the alveoli was greatly suppressed. However, inhibition of neutrophil infiltration of Th1 clones was very limited. None of the Th1-transfected mouse models showed significant improvement in respiratory indices.
As a result, the effect on cellular and respiratory indices is limited.
In addition, we observed that Th1, which is not dependent on antigen presentation, exhibited very high survival in response to steroids and molecularly targeted therapies. Thus, these findings suggest that Th1's antigen presentation-independent viability may be responsible for its refractoriness in asthma.
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| Free Research Field |
分子生物学
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| Academic Significance and Societal Importance of the Research Achievements |
我が国において、成人人口の3～4％の有病率とされる喘息は、新たな治療薬やガイドラインの改定が奏功しつつある一方、依然、年間おそよ2000人の死者をもたらす重大な疾患である。一方で、我が国で承認された新薬の15％は腫瘍用薬とその他の代謝性医薬品すなわちがん治療の医薬である。抗腫瘍の分子標的治療薬には、喘息と機序の一部を共通する細胞表面および細胞内シグナル経路ターゲットを持つものも含まれる。
我々は、複合的な喘息の病因・病態の中でもTh1細胞がマウス喘息モデルで難治性かつ重症化する性質を報告している。動物モデルから喘息治療への有効性を明らかにし、重症喘息治療への適応の足掛かりとなることが期待できる。
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