| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Outline of Final Research Achievements |
Alveolar macrophages (AMs) are specialized tissue-resident macrophages that orchestrate the immune responses to inhaled pathogens and maintain organ homeostasis of the lung, and dysregulation of AMs is associated with allergic inflammation and asthma. Here we show that mice with conditionally deleted PIKfyve, a phosphoinositide kinase with a FYVE finger, in macrophages displayed developmental arrest of AMs at the premature stage, and severe lung inflammation accompanied by infiltration of eosinophils and lymphoid cells after exposure to house dust mite extract. PIKfyve-deficient premature AMs had defects in production of retinoic acid, and failed both to support differentiation of Foxp3+ Treg cells and to suppress the Th2-type immune response. GM-CSF-mediated AMs differentiation was abrogated by PIKfyve deficiency, due to decreased AKT activation. These findings suggest that PIKfyve plays a critical role for AM development and maintenance of lung homeostasis.
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