Dörr D, Obermayer B, Weiner JM, Zimmermann K, Anania C, Wagner LK, Lyras EM, Sapozhnikova V, Lara-Astiaso D, Prósper F, Lang R, Lupiáñez DG, Beule D, Höpken UE, Leutz A, Mildner A (2022)
Publication Type: Journal article
Publication year: 2022
Book Volume: 7
Pages Range: eabj0140-
Journal Issue: 75
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.
APA:
Dörr, D., Obermayer, B., Weiner, J.M., Zimmermann, K., Anania, C., Wagner, L.K.,... Mildner, A. (2022). C/EBPβ regulates lipid metabolism and Pparg isoform 2 expression in alveolar macrophages. Science immunology, 7(75), eabj0140-. https://doi.org/10.1126/sciimmunol.abj0140
MLA:
Dörr, Dorothea, et al. "C/EBPβ regulates lipid metabolism and Pparg isoform 2 expression in alveolar macrophages." Science immunology 7.75 (2022): eabj0140-.
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