Detalle Publicación

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

Autores: Dorr, D.; Obermayer, B.; Weiner, J. M.; Zimmermann, K.; Anania, C.; Wagner, L. K.; Lyras, E. M.; Sapozhnikova, V.; LARA ASTIASO, David; Prosper Cardoso, Felipe; Lang, R.; Lupianez, D. G.; Beule, D.; Hopken, U. E.; Leutz, A.; Mildner, A. (Autor de correspondencia)
Título de la revista: SCIENCE IMMUNOLOGY
ISSN: 2470-9468
Volumen: 7
Número: 75
Páginas: eabj0140
Fecha de publicación: 2022
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 ss (C/EBP ss) is essential for the development of the AM identity, as demonstrated by transcriptome and chromatin accessibility analysis. Furthermore, C/EBP ss-deficient AMs showed severe defects in proliferation, phagocytosis, and lipid metabolism, collectively resulting in a PAP-like syndrome. Mechanistically, the long C/EBP ss 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/EBP ss as a key regulator of AM cell fate and shed light on the molecular networks controlling lipid metabolism in macrophages.