Mural cell-derived chemokines provide a protective niche to safeguard vascular macrophages and limit chronic inflammation

Pekayvaz, Kami; Gold, Christoph; Hoseinpour, Parandis; Engel, Anouk; Martinez-Navarro, Alejandro; Eivers, Luke; Coletti, Raffaele; Joppich, Markus; Dionisio, Flavio; Kaiser, Rainer; Tomas, Lukas; Janjic, Aleksandar; Knott, Maximilian; Mehari, Fitsumbirhan; Polewka, Vivien; Kirschner, Megan; Boda, Annegret; Nicolai, Leo; Schulz, Heiko; Titova, Anna; Kilani, Badr; Lorenz, Michael; Fingerle-Rowson, Gunter; Bucala, Richard; Enard, Wolfgang; Zimmer, Ralf; Weber, Christian; Libby, Peter; Schulz, Christian; Massberg, Steffen und Stark, Konstantin (2023): Mural cell-derived chemokines provide a protective niche to safeguard vascular macrophages and limit chronic inflammation. In: Immunity, Bd. 56, Nr. 10

Abstract

Maladaptive, non-resolving inflammation contributes to chronic inflammatory diseases such as atheroscle-rosis. Because macrophages remove necrotic cells, defective macrophage programs can promote chronic inflammation with persistent tissue injury. Here, we investigated the mechanisms sustaining vascular mac-rophages. Intravital imaging revealed a spatiotemporal macrophage niche across vascular beds alongside mural cells (MCs)-pericytes and smooth muscle cells. Single-cell transcriptomics, co-culture, and genetic deletion experiments revealed MC-derived expression of the chemokines CCL2 and MIF, which actively pre-served macrophage survival and their homeostatic functions. In atherosclerosis, this positioned macro-phages in viable plaque areas, away from the necrotic core, and maintained a homeostatic macrophage phenotype. Disruption of this MC-macrophage unit via MC-specific deletion of these chemokines triggered detrimental macrophage relocalizing, exacerbated plaque necrosis, inflammation, and atheroprogression. In line, CCL2 inhibition at advanced stages of atherosclerosis showed detrimental effects. This work presents a MC-driven safeguard toward maintaining the homeostatic vascular macrophage niche.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin > Munich Cluster for Systems Neurology (SyNergy)
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• Sprache: Englisch
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198