Histone deacetylase 1 and 2 play essential roles in alveolar macrophage homeostasis

Abstract

AbstractAlveolar macrophages (AMs) are the primary lung-resident macrophages that play a pivotal role in pathogen clearance and surfactant homeostasis. The precise molecular mechanisms that maintaining AM homeostasis remain incompletely understood. Histone deacetylase (HDAC) 1 and 2 are pleiotropic enzymes removing acetyl moieties from histone proteins, facilitating transcriptional repression via chromatin condensation.Hdac1andHdac2exhibit a broad tissue distribution and modulate various cellular processes across multiple tissues. In this study, we examined the role ofHdac1andHdac2in AM homeostasis. By usingCd11c-Cre andLyz2-Cre mouse strain to mediate deletion ofHdac1andHdac2in AMs, we found simultaneous loss of bothHdac1andHdac2caused profound defect of AMs. These HDACs deficient mice spontaneously developed pulmonary alveolar proteinosis syndrome and lost resistance to influenza virus. We further found up-regulation of pro-apoptotic proteins in AMs with HDACs defect, which caused apoptosis of AM. Taken together, these observations shed light on the roles ofHdac1andHdac2as key epigenetic regulators in maintaining integrity of the AMs.