Analysis of exacerbation of allergic skin inflammation

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07460
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49030:Experimental pathology-related
• Research Institution: National Center for Global Health and Medicine
• 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)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: アレルギー性皮膚炎 / IL-33

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.

Free Research Field

免疫学

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。