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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., Obermayer, B., Weiner, J.M., Zimmermann, K., Anania, C., Wagner, L.K., Lyras, E.M., Sapozhnikova, V., Lara-Astiaso, D., Prósper, F., Lang, R., Lupiáñez, D.G., Beule, D., Höpken, U.E., 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 |
| ISSN: | 2470-9468 |
| Publisher: | American Association for the Advancement of Science |
| Volume: | 7 |
| Number: | 75 |
| 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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