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C/EBPβ regulates lipid metabolism and Pparg isoform 2 expression in alveolar macrophages

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Item Type:Article
Title:C/EBPβ regulates lipid metabolism and Pparg isoform 2 expression in alveolar macrophages
Creators Name:Dörr, D. and Obermayer, B. and Weiner, J.M. and Zimmermann, K. and Anania, C. and Wagner, L.K. and Lyras, E.M. and Sapozhnikova, V. and Lara-Astiaso, D. and Prósper, F. and Lang, R. and Lupiáñez, D.G. and Beule, D. and Höpken, U.E. and Leutz, A. and Mildner, A.
Abstract: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.
Keywords:Chromatin, Lipid Metabolism, Lipoproteins, Alveolar Macrophages, PPAR gamma, Protein Isoforms, Pulmonary Surfactants, Surface-Active Agents
Source:Science Immunology
Publisher:American Association for the Advancement of Science
Page Range:eabj0140
Date:September 2022
Additional Information:Copyright © 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
Official Publication:https://doi.org/10.1126/sciimmunol.abj0140
PubMed:View item in PubMed

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