Kawasaki Takumi, Ito Kosuke, Miyata Haruhiko, Akira Shizuo, Kawai Taro
Laboratory of Molecular Immunobiology, Graduate School of Biological Sciences, Nara Institute of Science and Technology (NAIST), Nara, Japan
Laboratory of Molecular Immunobiology, Graduate School of Biological Sciences, Nara Institute of Science and Technology (NAIST), Nara, Japan.
EMBO J. 2017 Jun 14;36(12):1707-1718. doi: 10.15252/embj.201695528. Epub 2017 May 22.
Alveolar macrophages (AMs) are specialized tissue-resident macrophages that orchestrate the immune responses to inhaled pathogens and maintain organ homeostasis of the lung. Dysregulation of AMs is associated with allergic inflammation and asthma. Here, we examined the role of a phosphoinositide kinase PIKfyve in AM development and function. Mice with conditionally deleted PIKfyve in macrophages have altered AM populations. PIKfyve deficiency results in a loss of AKT activation in response to GM-CSF, a cytokine critical for AM development. Upon exposure to house dust mite extract, mutant mice display severe lung inflammation and allergic asthma accompanied by infiltration of eosinophils and lymphoid cells. Moreover, they have defects in production of retinoic acid and fail to support incorporation of Foxp3 T cells in the lung, resulting in exacerbation of lung inflammation. Thus, PIKfyve plays a role in preventing excessive lung inflammation through regulating AM function.
肺泡巨噬细胞（AMs）是专门驻留在组织中的巨噬细胞，可协调对吸入病原体的免疫反应并维持肺部器官的内环境稳定。AMs失调与过敏性炎症和哮喘有关。在此，我们研究了磷酸肌醇激酶PIKfyve在AMs发育和功能中的作用。巨噬细胞中条件性缺失PIKfyve的小鼠，其AMs群体发生了改变。PIKfyve缺乏导致对GM-CSF（一种对AMs发育至关重要的细胞因子）的反应中AKT激活丧失。暴露于屋尘螨提取物后，突变小鼠表现出严重的肺部炎症和过敏性哮喘，并伴有嗜酸性粒细胞和淋巴细胞浸润。此外，它们在视黄酸产生方面存在缺陷，并且无法支持Foxp3 T细胞在肺中的掺入，从而导致肺部炎症加剧。因此，PIKfyve通过调节AMs功能在预防过度肺部炎症中发挥作用。
