Dataset Information

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

ABSTRACT: Maladaptive, non-resolving inflammation contributes to chronic inflammatory diseases such as atherosclerosis. Because macrophages remove necrotic cells, defective macrophage programs can promote chronic inflammation with persistent tissue injury. Here, we investigated the mechanisms sustaining vascular macrophages. 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 preserved macrophage survival and their homeostatic functions. In atherosclerosis, this positioned macrophages 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.

SUBMITTER: Pekayvaz K

PROVIDER: S-EPMC10588993 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Pekayvaz Kami K Gold Christoph C Hoseinpour Parandis P Engel Anouk A Martinez-Navarro Alejandro A Eivers Luke L Coletti Raffaele R Joppich Markus M Dionísio Flávio F Kaiser Rainer R Tomas Lukas L Janjic Aleksandar A Knott Maximilian M Mehari Fitsumbirhan F Polewka Vivien V Kirschner Megan M Boda Annegret A Nicolai Leo L Schulz Heiko H Titova Anna A Kilani Badr B Lorenz Michael M Fingerle-Rowson Günter G Bucala Richard R Enard Wolfgang W Zimmer Ralf R Weber Christian C Libby Peter P Schulz Christian C Massberg Steffen S Stark Konstantin K

Immunity 20230830 10

Maladaptive, non-resolving inflammation contributes to chronic inflammatory diseases such as atherosclerosis. Because macrophages remove necrotic cells, defective macrophage programs can promote chronic inflammation with persistent tissue injury. Here, we investigated the mechanisms sustaining vascular macrophages. Intravital imaging revealed a spatiotemporal macrophage niche across vascular beds alongside mural cells (MCs)-pericytes and smooth muscle cells. Single-cell transcriptomics, co-cultu ...[more]

PMID: 37652021

Similar Datasets

Project description:Macrophages have a key role in shaping the tumour microenvironment (TME), tumour immunity and response to immunotherapy, which makes them an important target for cancer treatment1,2. However, modulating macrophages has proved extremely difficult, as we still lack a complete understanding of the molecular and functional diversity of the tumour macrophage compartment. Macrophages arise from two distinct lineages. Tissue-resident macrophages self-renew locally, independent of adult haematopoiesis3-5, whereas short-lived monocyte-derived macrophages arise from adult haematopoietic stem cells, and accumulate mostly in inflamed lesions1. How these macrophage lineages contribute to the TME and cancer progression remains unclear. To explore the diversity of the macrophage compartment in human non-small cell lung carcinoma (NSCLC) lesions, here we performed single-cell RNA sequencing of tumour-associated leukocytes. We identified distinct populations of macrophages that were enriched in human and mouse lung tumours. Using lineage tracing, we discovered that these macrophage populations differ in origin and have a distinct temporal and spatial distribution in the TME. Tissue-resident macrophages accumulate close to tumour cells early during tumour formation to promote epithelial-mesenchymal transition and invasiveness in tumour cells, and they also induce a potent regulatory T cell response that protects tumour cells from adaptive immunity. Depletion of tissue-resident macrophages reduced the numbers and altered the phenotype of regulatory T cells, promoted the accumulation of CD8+ T cells and reduced tumour invasiveness and growth. During tumour growth, tissue-resident macrophages became redistributed at the periphery of the TME, which becomes dominated by monocyte-derived macrophages in both mouse and human NSCLC. This study identifies the contribution of tissue-resident macrophages to early lung cancer and establishes them as a target for the prevention and treatment of early lung cancer lesions.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets