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Article ; Online: C/EBPβ regulates lipid metabolism and

Dörr, Dorothea / Obermayer, Benedikt / Weiner, January Mikolaj / Zimmermann, Karin / Anania, Chiara / Wagner, Lisa Katharina / Lyras, Ekaterini Maria / Sapozhnikova, Valeriia / Lara-Astiaso, David / Prósper, Felipe / Lang, Roland / Lupiáñez, Darío G / Beule, Dieter / Höpken, Uta E / Leutz, Achim / Mildner, Alexander

Science immunology

2022  Volume 7, Issue 75, Page(s) eabj0140

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 ... ...

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
MeSH term(s) Chromatin/metabolism ; Lipid Metabolism ; Lipoproteins/metabolism ; Macrophages, Alveolar/metabolism ; PPAR gamma/metabolism ; Protein Isoforms/metabolism ; Pulmonary Surfactants/metabolism ; Surface-Active Agents/metabolism
Chemical Substances Chromatin ; Lipoproteins ; PPAR gamma ; Protein Isoforms ; Pulmonary Surfactants ; Surface-Active Agents
Language English
Publishing date 2022-09-16
Publishing country United States
Document type Journal Article ; Research Support, Non-U.S. Gov't
ISSN 2470-9468
ISSN (online) 2470-9468
DOI 10.1126/sciimmunol.abj0140
Database MEDical Literature Analysis and Retrieval System OnLINE

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