Investigation of the mechanism of secondary PAP using Bach2-deficient mice

2017 Fiscal Year Final Research Report

• Project/Area Number: 16H06640
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Respiratory organ internal medicine
• Research Institution: Tohoku University
• Principal Investigator: Shibuya Risa 東北大学, 医学系研究科, 非常勤講師 (90778408)
• Project Period (FY): 2016-08-26 – 2018-03-31
• Keywords: 肺胞蛋白症 / 肺胞マクロファージ / Bach2 / Bach1 / 免疫 / 炎症

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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