Similar Datasets
Project description:Macrophages are considered to contribute to chronic inflammatory diseases such as rheumatoid arthritis1. However, both the exact origin and the role of macrophages in inflammatory joint disease remain unclear. Here we use fate-mapping approaches in conjunction with three-dimensional light-sheet fluorescence microscopy and single-cell RNA sequencing to perform a comprehensive spatiotemporal analysis of the composition, origin and differentiation of subsets of macrophages within healthy and inflamed joints, and study the roles of these macrophages during arthritis. We find that dynamic membrane-like structures, consisting of a distinct population of CX3CR1+ tissue-resident macrophages, form an internal immunological barrier at the synovial lining and physically seclude the joint. These barrier-forming macrophages display features that are otherwise typical of epithelial cells, and maintain their numbers through a pool of locally proliferating CX3CR1- mononuclear cells that are embedded into the synovial tissue. Unlike recruited monocyte-derived macrophages, which actively contribute to joint inflammation, these epithelial-like CX3CR1+ lining macrophages restrict the inflammatory reaction by providing a tight-junction-mediated shield for intra-articular structures. Our data reveal an unexpected functional diversification among synovial macrophages and have important implications for the general role of macrophages in health and disease.
| S-EPMC6805223 | biostudies-literature
Project description:Macrophages (MΦs) are considered to contribute to chronic inflammatory diseases such as rheumatoid arthritis 1. However, both the exact origin and role of MΦs during inflammatory joint disease remain unclear. Here, we used multiple fate-mapping approaches in conjunction with 3D-light-sheet fluorescence microscopy and single cell RNA sequencing to perform a comprehensive spatiotemporal analysis of the composition, origin and differentiation of MΦ subsets within the healthy and inflamed joint and subsequently studied their roles during arthritis. This approach revealed dynamic membrane-like structures consisting of a distinct population of CX3CR1+ tissue-resident MΦs that formed an internal immunological barrier at the synovial lining and physically secluded the joint. Barrier-forming MΦs displayed features otherwise typical of epithelial cells, and maintained their numbers through a pool of locally proliferating CX3CR1- mononuclear cells embedded into the synovial tissue. Unlike recruited monocyte-derived MΦs, which actively contributed to joint inflammation, such epithelial-like CX3CR1+ lining MΦs restricted the inflammatory reaction by providing a tight junction-mediated shield for intra-articular structures. Our data thus reveal an unexpected functional diversification among synovial MΦs and have important implications for the general role of MΦs in health and disease
2019-08-07 | GSE134420 | GEO
Project description:Macrophages (MΦs) are considered to contribute to chronic inflammatory diseases such as rheumatoid arthritis 1. However, both the exact origin and role of MΦs during inflammatory joint disease remain unclear. Here, we used multiple fate-mapping approaches in conjunction with 3D-light-sheet fluorescence microscopy and single cell RNA sequencing to perform a comprehensive spatiotemporal analysis of the composition, origin and differentiation of MΦ subsets within the healthy and inflamed joint and subsequently studied their roles during arthritis. This approach revealed dynamic membrane-like structures consisting of a distinct population of CX3CR1+ tissue-resident MΦs that formed an internal immunological barrier at the synovial lining and physically secluded the joint. Barrier-forming MΦs displayed features otherwise typical of epithelial cells, and maintained their numbers through a pool of locally proliferating CX3CR1- mononuclear cells embedded into the synovial tissue. Unlike recruited monocyte-derived MΦs, which actively contributed to joint inflammation, such epithelial-like CX3CR1+ lining MΦs restricted the inflammatory reaction by providing a tight junction-mediated shield for intra-articular structures. Our data thus reveal an unexpected functional diversification among synovial MΦs and have important implications for the general role of MΦs in health and disease.
2019-08-07 | GSE134286 | GEO
Project description:Locally renewing resident synovial macrophages provide a protective barrier for the joint
| PRJNA556088 | ENA
Project description:Locally renewing resident synovial macrophages provide a protective barrier for the joint [RNA-seq]
| PRJNA554646 | ENA
Project description:Locally renewing resident synovial macrophages provide a protective barrier for the joint [scRNA-seq]
| PRJNA555105 | ENA
Project description:Macrophages promote both injury and repair after myocardial infarction, but discriminating functions within mixed populations remains challenging. Here we used fate mapping, parabiosis and single-cell transcriptomics to demonstrate that at steady state, TIMD4+LYVE1+MHC-IIloCCR2- resident cardiac macrophages self-renew with negligible blood monocyte input. Monocytes partially replaced resident TIMD4-LYVE1-MHC-IIhiCCR2- macrophages and fully replaced TIMD4-LYVE1-MHC-IIhiCCR2+ macrophages, revealing a hierarchy of monocyte contribution to functionally distinct macrophage subsets. Ischemic injury reduced TIMD4+ and TIMD4- resident macrophage abundance, whereas CCR2+ monocyte-derived macrophages adopted multiple cell fates within infarcted tissue, including those nearly indistinguishable from resident macrophages. Recruited macrophages did not express TIMD4, highlighting the ability of TIMD4 to track a subset of resident macrophages in the absence of fate mapping. Despite this similarity, inducible depletion of resident macrophages using a Cx3cr1-based system led to impaired cardiac function and promoted adverse remodeling primarily within the peri-infarct zone, revealing a nonredundant, cardioprotective role of resident cardiac macrophages.
| S-EPMC6565365 | biostudies-literature
Project description:ObjectivesResident synovial macrophages (RSM) provide immune sequestration of the joint space and are likely involved in initiation and perpetuation of the joint-specific immune response. We sought to identify RSM in synovial fluid (SF) and demonstrate migratory ability, in additional to functional changes that may perpetuate a chronic inflammatory response within joint spaces.MethodsWe recruited human patients presenting with undifferentiated arthritis in multiple clinical settings. We used flow cytometry to identify mononuclear cells in peripheral blood and SF. We used a novel transwell migration assay with human ex-vivo synovium obtained intra-operatively to validate flow cytometry findings. We used single cell RNA-sequencing (scRNA-seq) to further identify macrophage/monocyte subsets. ELISA was used to evaluate the bone-resorption potential of SF.ResultsWe were able to identify a rare population of CD14dim, OPG+, ZO-1+ cells consistent with RSM in SF via flow cytometry. These cells were relatively enriched in the SF during infectious processes, but absolutely decreased compared to healthy controls. Similar putative RSM were identified using ex vivo migration assays when MCP-1 and LPS were used as migratory stimulus. scRNA-seq revealed a population consistent with RSM transcriptionally related to CD56+ cytotoxic dendritic cells and IDO+ M2 macrophages.ConclusionWe identified a rare cell population consistent with RSM, indicating these cells are likely migratory and able to initiate or coordinate both acute (septic) or chronic (autoimmune or inflammatory) arthritis. RSM analysis via scRNA-seq indicated these cells are M2 skewed, capable of antigen presentation, and have consistent functions in both septic and inflammatory arthritis.
| S-EPMC10592878 | biostudies-literature
Project description:Adult tissue-resident macrophages (RMs) are either maintained by blood monocytes or through self-renewal. While the presence of a nurturing niche is likely crucial to support the survival and function of self-renewing RMs, evidence regarding its nature is limited. Here, we identify fibro-adipogenic progenitors (FAPs) as the main source of colony-stimulating factor 1 (CSF1) in resting skeletal muscle. Using parabiosis in combination with FAP-deficient transgenic mice (PdgfrαCreERT2 × DTA) or mice lacking FAP-derived CSF1 (PdgfrαCreERT2 × Csf1flox/null), we show that local CSF1 from FAPs is required for the survival of both TIM4- monocyte-derived and TIM4+ self-renewing RMs in adult skeletal muscle. The spatial distribution and number of TIM4+ RMs coincide with those of dipeptidyl peptidase IV (DPPIV)+ FAPs, suggesting their role as CSF1-producing niche cells for self-renewing RMs. This finding identifies opportunities to precisely manipulate the function of self-renewing RMs in situ to further unravel their role in health and disease.
| S-EPMC10719395 | biostudies-literature
Project description:Although apoptotic cells (ACs) contain nucleic acids that can be recognized by Toll-like receptors (TLRs), engulfment of ACs does not initiate inflammation in healthy organisms. Here we identified macrophage populations that continually engulf ACs in distinct tissues and found that these macrophages share characteristics compatible with immunologically silent clearance of ACs; such characteristics include high expression of AC recognition receptors, low expression of TLR9, and reduced TLR responsiveness to nucleic acids. Removal of the macrophages from tissues resulted in loss of many of these characteristics and the ability to generate inflammatory responses to AC-derived nucleic acids, suggesting that cues from the tissue microenvironment program macrophages for silent AC clearance. The transcription factors KLF2 and KLF4 control the expression of many genes within this AC clearance program. The coordinated expression of AC receptors with genes that limit responses to nucleic acids might ensure maintenance of homeostasis and thus represent a central feature of tissue macrophages.
| S-EPMC5728676 | biostudies-literature