2022 Fiscal Year Final Research Report
Role of Treg cells in the development of allergic airway inflammation
Project/Area Number |
20K08768
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 54020:Connective tissue disease and allergy-related
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Research Institution | Chiba University |
Principal Investigator |
Akira Suto 千葉大学, 大学院医学研究院, 准教授 (50447306)
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Co-Investigator(Kenkyū-buntansha) |
田中 繁 千葉大学, 医学部附属病院, 助教 (30822051)
岩田 有史 千葉大学, 大学院医学研究院, 助教 (90436353)
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Project Period (FY) |
2020-04-01 – 2023-03-31
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Keywords | Sox4 / c-Maf / Asthma / Treg |
Outline of Final Research Achievements |
Bronchial asthma is a chronic allergic inflammation of the airways and is characterized by infiltration of eosinophils and Th2 cells into the airways. It has been shown that IL-10 produced by regulatory T (Treg) cells plays an important role in suppressing allergic airway inflammation, and that the transcription factor c-Maf binds to the Il10 gene locus and positively regulates IL-10 production. However, the precise mechanisms of IL-10 production from Treg cells were still largely unknown. Here, we show that Sox4-deficeient Treg cells enhance c-Maf expression and IL-10 production, and that the Treg-specific Sox4-deficient mice exhibited significantly lower Th2 cells and eosinophil infiltration into the airways upon allergic airway inflammation. The C-terminal of Sox4, which contains the PEST sequences, promotes proteasome-dependent degradation of c-Maf in Treg cells. These results add new insight into the mechanisms of Treg cell mediated suppression of allergic airway inflammation.
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Free Research Field |
アレルギー、自己免疫
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Academic Significance and Societal Importance of the Research Achievements |
気管支喘息は人口の約6%が罹患する最も有病率の高いアレルギー性呼吸器疾患である。吸入ステロイド薬に加え、IgE、IL-5、IL-4/IL-13, TSLPを標的とした抗体医薬が開発・臨床応用され、治療選択肢は増えたが、未だに治療困難な症例が多数存在する。本研究ではアレルギー性気道炎症局所に存在する制御性T細胞に発現するSox4がc-Mafの発現を抑制し、IL-10の産生を抑制することにより気管支喘息を増悪させることを明らかにした。これら結果は喘息の制御機構における新たな知見であり学術的・臨床的に意義の大きい研究と考えられる。
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