Back

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

Lai, W.; Luo, M.; Li, X.; He, Z.; Wu, T.; Wu, L.

2024-05-09 immunology
10.1101/2024.05.06.590855 bioRxiv
Show 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. Hdac1 and Hdac2 exhibit a broad tissue distribution and modulate various cellular processes across multiple tissues. In this study, we examined the role of Hdac1 and Hdac2 in AM homeostasis. By using Cd11c-Cre and Lyz2-Cre mouse strain to mediate deletion of Hdac1 and Hdac2 in AMs, we found simultaneous loss of both Hdac1 and Hdac2 caused 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 of Hdac1 and Hdac2 as key epigenetic regulators in maintaining integrity of the AMs.

Matching journals

The top 4 journals account for 50% of the predicted probability mass.

50% of probability mass above

"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.