A1 Refereed original research article in a scientific journal
C/EBPβ regulates lipid metabolism and Pparg isoform 2 expression in alveolar macrophages
Authors: Dörr Dorothea, Obermayer Benedikt, Weiner January Mikolaj, Zimmermann Karin, Anania Chiara, Wagner Lisa Katharina, Lyras Ekaterina Maria, Sapozhnikova Valeriia, Lara-Astiaso David, Prósper Felipe, Lang Roland, Lupiáñez Dario G, Beule Dieter, Höpken Uta E, Leutz Achim, Mildner Alexander
Publisher: American Association for the Advancement of Science
Publication year: 2022
Journal: Science Immunology
Journal name in source: Science immunology
Journal acronym: Sci Immunol
Article number: eabj014
Volume: 7
Issue: 75
ISSN: 2470-9468
eISSN: 2470-9468
DOI: https://doi.org/10.1126/sciimmunol.abj0140
Publication's open availability at the time of reporting: No Open Access
Publication channel's open availability : Partially Open Access publication channel
Web address : https://www.science.org/doi/10.1126/sciimmunol.abj0140
Pulmonary alveolar proteinosis (PAP) is a syndrome characterized by accumulation of surfactant lipoproteins within the lung alveoli. Alveolar macrophages (AMs) are crucial for surfactant clearance, and their differentiation depends on colony-stimulating factor 2 (CSF2), which regulates the establishment of an AM-characteristic gene regulatory network. Here, we report that the transcription factor CCAAT/enhancer binding protein β (C/EBPβ) is essential for the development of the AM identity, as demonstrated by transcriptome and chromatin accessibility analysis. Furthermore, C/EBPβ-deficient AMs showed severe defects in proliferation, phagocytosis, and lipid metabolism, collectively resulting in a PAP-like syndrome. Mechanistically, the long C/EBPβ protein variants LAP* and LAP together with CSF2 signaling induced the expression of Pparg isoform 2 but not Pparg isoform 1, a molecular regulatory mechanism that was also observed in other CSF2-primed macrophages. These results uncover C/EBPβ as a key regulator of AM cell fate and shed light on the molecular networks controlling lipid metabolism in macrophages.
