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

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

Journal

Science immunology American Association for the Advancement of Science

Book Volume: 7

Pages Range: eabj0140-

Journal Issue: 75

DOI: 10.1126/sciimmunol.abj0140

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.

Authors with CRIS profile

Roland Lang Professur für Angeborene Immunität und Pathogenerkennung

Involved external institutions

Max-Delbrück-Centrum für Molekulare Medizin / Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch DE Germany (DE) Berliner Institut für Gesundheitsforschung (BIH) DE Germany (DE) Universidad de Navarra ES Spain (ES)

How to cite

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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