| Project/Area Number |
16H06640
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Single-year Grants |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | Tohoku University |
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Principal Investigator |
Shibuya Risa 東北大学, 医学系研究科, 非常勤講師 (90778408)
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| Project Period (FY) |
2016-08-26 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 肺胞蛋白症 / 肺胞マクロファージ / Bach2 / Bach1 / 免疫 / 炎症 / 続発性肺胞蛋白症 / 慢性炎症 / 免疫学 / 遺伝子 / 発現制御 |
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| Outline of Final Research Achievements |
Using mice lacking Bach2 in specific cell types, we found that the Pulmonary alveolar proteinosis (PAP)-phenotype of Bach2-deficient mice is due to Bach2 deficiency in more than two types of immune cells. Depletion of hyper-activated T cells in Bach2-deficient mice restored normal function of alveolar macrophages (AMs) and ameliorated PAP. Hyperactivated T cells induced gene expression patterns that are specific to other tissue-resident macrophages and dendritic cells in AMs, in which Bach2 then bound to regulatory regions of these genes. We conclude that Bach2 is critical for the maintenance of AM identity in inflammatory environments.
The Bach1/Bach2 double-deficient mice showed a more rapid and severe PAP phenotype than Bach2-deficient mice with abnormal AMs, whereas the Bach1-deficient mice did not develop any pulmonary disease. Bach1 and Bach2 work in a complementary manner to maintain the normal function of the AMs and surfactant homeostasis in the lung.
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