Deletion of PIKfyve alters alveolar macrophage populations and exacerbates allergic inflammation in mice

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+ Treg cells in the lung, resulting in exacerbation of lung inflammation. Thus, PIKfyve plays a role in preventing excessive lung inflammation through regulating AM function.

Keywords: alveolar macrophage; anti‐inflammatory response; inositol lipid; lipid kinase; macrophage development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allergens / administration & dosage
  • Animals
  • Asthma / pathology*
  • Gene Knockout Techniques
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
  • Hypersensitivity / pathology*
  • Inflammation / pathology*
  • Lung / pathology
  • Macrophages, Alveolar / physiology*
  • Mice
  • Mice, Knockout
  • Phosphatidylinositol 3-Kinases / deficiency
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Sequence Deletion
  • Signal Transduction
  • T-Lymphocytes, Regulatory / immunology


  • Allergens
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Phosphatidylinositol 3-Kinases
  • Pikfyve protein, mouse