Lung epithelial cells regulate ILC2 homeostasis
Project/Area Number |
18H02647
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Review Section |
Basic Section 49030:Experimental pathology-related
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Research Institution | Akita University (2019-2020) Institute of Physical and Chemical Research (2018) |
Principal Investigator |
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Project Period (FY) |
2018-04-01 – 2021-03-31
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Project Status |
Completed (Fiscal Year 2020)
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Budget Amount *help |
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2020: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2019: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2018: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
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Keywords | ILC2 / Runx / 疲弊様現象 / 肺内環境 / 2型自然リンパ球 / 慢性アレルギー炎症 / 分化微小環境 / 慢性閉塞性肺疾患 / 喘息 |
Outline of Final Research Achievements |
Group 2 innate lymphoid cells (ILC2s) preferentially develop in the lung and contribute to acute allergic inflammation. We clarified physiological roles of transcription factor family Runx proteins in regulating ILC2 homeostasis and activity in a cell-intrinsic or cell-extrinsic manner. ILC2s deficient for Runx protein function fell into exhausted-like low reactivity during severe allergic airway inflammation, leading to decreased allergic inflammation mediated by decreased eosinophil recruitment. We also identified exhausted-like ILC2s expressing Tigit and IL-10 in airways of wild type mice with severe and chronic allergy. Furthermore, Runx deficiency in lung epithelial cells or stromal cells decreased ILC2 number in the lung. Our data also suggested that Runx proteins in epithelial cells are involved in the reduction of lung ILC2s. Thus, Runx proteins are key transcription factors in the maintenance of ILC2 activity and number in the lung.
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Academic Significance and Societal Importance of the Research Achievements |
ILC2は、アレルギー炎症によっていくつかの亜集団に分かれることは分かっていたが、未だに活性化したILC2の運命決定機構は明らかになっていない。私達は、激しいアレルギー炎症状態においてILC2が疲弊様現象をきたすことを初めて明らかにした。そして転写因子Runxが疲弊様現象を抑制しているという結果は、アレルギー炎症を制御する上で重要な発見である。また、ILC2肺内環境に上皮細胞の転写因子Runxが影響を与えるという結果は、気管支喘息誘導機序を解き明かす一助になる発見である。
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Report
(4 results)
Research Products
(15 results)
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[Journal Article] Group 3 Innate Lymphoid Cells Mediate Early Protective Immunity Against Tuberculosis2019
Author(s)
Ardain A, Domingo-Gonzalez R, Das S,,,Ebihara T,,,Colonna M, Leslie A, Khader SA.
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Journal Title
Nature
Volume: 570
Issue: 7762
Pages: 528-532
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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