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

Alveolar macrophages ( AM s) are specialized tissue‐resident macrophages that orchestrate the immune responses to inhaled pathogens and maintain organ homeostasis of the lung. Dysregulation of AM s is associated with allergic inflammation and asthma. Here, we examined the role of a phosphoinositide kinase PIK fyve in AM development and function. Mice with conditionally deleted PIK fyve in macrophages have altered AM populations. PIK fyve 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 reg cells in the lung, resulting in exacerbation of lung inflammation. Thus, PIK fyve plays a role in preventing excessive lung inflammation through regulating AM function.