Analysis of exacerbation of allergic skin inflammation
| Project/Area Number |
20K07460
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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 49030:Experimental pathology-related
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| Research Institution | National Center for Global Health and Medicine |
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Principal Investigator |
Kitajima Masayuki 国立研究開発法人国立国際医療研究センター, その他部局等, 上級研究員 (00401000)
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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 |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | アレルギー性皮膚炎 / IL-33 / 化学的刺激 / 物理的刺激 |
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| Outline of Research at the Start |
本研究では、アレルギー性皮膚炎症の多因子相乗作用によって生じる複合的かつ重篤な炎症増悪化メカニズムを理解するために新規炎症増悪化モデルを構築する。特にアレルギー性皮膚炎症の増悪化に関与すると報告されているTSLPとIL-33に着目する。具体的には①アレルゲン（TSLP誘導因子）と強い化学的ストレス（IL-33誘導因子）、②アレルゲンと物理的ストレス（IL-33誘導因子）、③アレルゲンと強い化学的・物理的ストレスを併せた刺激によって生じる重篤な炎症増悪化メカニズムの解析の３点について研究を実施する。
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| Outline of Final Research Achievements |
Atopic dermatitis (AD) is one of the chronic inflammatory skin diseases characterized by type 2 inflammation, impaired skin barrier, and intense itching. The pathogenesis of AD is involved in genetic and environmental factors. The complexity of human AD is not fully reproduced by available animal models. IL-33 is a newly cytokine, and is secreted from inflamed and damaged tissues may be involved in the pathogenesis of AD, but the role of IL-33 in AD is unresolved. To understand the exacerbation factors in skin inflammation, we established novel skin inflammation models using hapten (allergen, Th2 inducer) combined with physical stress (tape stripping) or chemical stress (surfactant, irritant). We found that ST2 (IL-33 receptor)-deficient (KO) mice were reduced skin inflammation in these models, but not hapten-induced inflammation. These results suggest that IL-33 has a novel role for promoting skin inflammation as an exacerbation factor.
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| Academic Significance and Societal Importance of the Research Achievements |
申請者は、アレルゲンと物理的刺激もしくは化学的刺激を複合的に組み合わせた新規皮膚炎症増悪化モデルマウスを構築した。さらにアトピー性皮膚炎病態との関連がみられるIL-33の受容体ST2を欠損したマウスを用いた解析から、IL-33がこれらのマウスモデルの皮膚炎増悪化因子の一つであることを明らかにした。本研究成果は、新たな炎症増悪化メカニズムの理解と根治治療法開発に向けた基礎研究基盤となることが期待される。
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Report
(4 results)
Research Products
(4 results)
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[Journal Article] Epithelial cell-derived cytokine TSLP modulates metabolic program of regulatory T cells by enhancing fatty acid uptake to suppress the intestinal inflammation2023
Author(s)
Kasuya T., Tanaka S., Etori K., Shoda J., Hattori K., Endo Y., Kitajima M., Kageyama T., Iwamoto T., Yokota M., Iwata A., Suto A., Suzuki K., Suzuki H., Ziegler SF., and Nakajima H
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Journal Title
Sci. Rep.
Volume: 13
Issue: 1
Pages: 1653-1653
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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