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2020 Fiscal Year Final Research Report

Contribution of ST2+CD4+ T cells in the mechanism of steroid-resistant asthma

Research Project

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Project/Area Number 18K08152
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53030:Respiratory medicine-related
Research InstitutionJichi Medical University

Principal Investigator

Mato Naoko  自治医科大学, 医学部, 准教授 (80406149)

Co-Investigator(Kenkyū-buntansha) 平原 潔  千葉大学, 大学院医学研究院, 准教授 (00707193)
Project Period (FY) 2018-04-01 – 2021-03-31
KeywordsIL-33 / ST2陽性Th2細胞 / ステロイド抵抗性喘息 / ステロイド血中濃度
Outline of Final Research Achievements

Interleukin (IL-)33 drives the type 2 immune response by activating ST2-expressed immune cells. Here we found that IL-33 induced the increase of numbers of ST2+Th2 cells in the lung and production of IL-5 and IL-13 , and drove asthma-like reaction. IL-33-mediated inflammation was not fully developed in T cell-deficient mice, and dexamethasone treatment showed limited effects on ST2+Th2 cells. Our study showed that ST2+ Th2 cells contributed to the pathogenesis of steroid-resistant refractory asthma. In addition, IL-33-induced MAPK activation was considered to inhibit the cellular translocation of glucocorticoid receptor(GR) and GR-associated signal transduction. Finally, we investigated the correlation between steroid-resistance and plasma concentration of oral corticosteroid. We discovered plasma levels were negatively correlated with body weight and BMI. Therefore, true effective dose of corticosteroid should be taken into consideration in the refractory asthma patients.

Free Research Field

呼吸器

Academic Significance and Societal Importance of the Research Achievements

ステロイド抵抗性喘息の中心となる細胞や機序は不明であった。申請者は本研究でその機序に迫り、気道上皮下層に常在するST2陽性Th2細胞が、気道上皮細胞より放出されるInterleukin-33 (IL-33)に反応してステロイド抵抗性の好酸球性炎症を惹起することを見出した。IL-33シグナルおよびST2陽性Th2細胞は、難治性病態であるステロイド抵抗性病態の治療標的になると考えられた。また本研究によりBMI、体重増加が経口ステロイドの血中濃度を低下させ効果を減弱する可能性が示された。ステロイド抵抗性病態において、本研究は新たな治療標的と薬物代謝という新しい視点を提示したと考える。

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Published: 2022-01-27  

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