Similar Datasets
Project description:The interactions between chemokines and their receptors, particularly in the context of inflammation, are complex, with individual receptors binding multiple ligands and individual ligands interacting with multiple receptors. In addition, there are numerous reports of simultaneous coexpression of multiple inflammatory chemokine receptors on individual inflammatory leukocyte subtypes. Overall, this has previously been interpreted as redundancy and proposed as a protective mechanism to ensure that the inflammatory response is robust. By contrast, we have hypothesized that the system is not redundant but exquisitely subtle. Our interests relate to the receptors CCR1, CCR2, CCR3, and CCR5, which, together, regulate nonneutrophilic myeloid cell recruitment to inflammatory sites. In this study, we demonstrate that although most murine monocytes exclusively express CCR2, there is a small subpopulation that is expanded during inflammation and coexpresses CCR1 and CCR2. Combinations of transcript and functional analysis demonstrate that this is not redundant expression and that coexpression of CCR1 and CCR2 marks a phenotypically distinct population of monocytes characterized by expression of genes otherwise typically associated with neutrophils. Single-cell RNA sequencing confirms this as a monodisperse population of atypical monocytes. This monocytic population has previously been described as having immunosuppressive activity. Overall, our data confirm combinatorial chemokine receptor expression by a subpopulation of monocytes but demonstrate that this is not redundant expression and marks a discrete monocytic population.
| S-EPMC11215633 | biostudies-literature
Project description:The interactions between chemokines and their receptors, particularly in the context of inflammation, are complex with individual receptors binding multiple ligands and individual ligands interacting with multiple receptors. In addition, there are numerous reports of simultaneous co-expression of multiple inflammatory chemokine receptors on individual inflammatory leukocyte subtypes. Overall, this has previously been interpreted as redundancy and proposed as a protective mechanism to ensure that the inflammatory response is robust. In contrast we have hypothesised that the system is not redundant but exquisitely subtle. Our interests relate to the receptors CCR1, CCR2, CCR3 and CCR5 which, together, regulate non-neutrophilic myeloid cell recruitment to inflammatory sites. Here we demonstrate that, whilst most murine monocytes exclusively express CCR2, there is a small subpopulation, which is expanded during inflammation, which co-expresses CCR1 and CCR2. Combinations of transcript and functional analysis demonstrate that this is not redundant expression and that co-expression of CCR1 and CCR2 marks a phenotypically distinct population of monocytes characterised by expression of genes otherwise typically associated with neutrophils. Single cell RNA sequencing confirms this as a monodisperse population of atypical monocytes. This monocytic population has been previously described as having immunosuppressive activity. Overall, our data confirm combinatorial chemokine receptor expression by a subpopulation of monocytes but demonstrate that this is not redundant expression and marks a discrete monocytic population.
2024-07-10 | GSE251646 | GEO
Project description:The interactions between chemokines and their receptors, particularly in the context of inflammation, are complex with individual receptors binding multiple ligands and individual ligands interacting with multiple receptors. In addition, there are numerous reports of simultaneous co-expression of multiple inflammatory chemokine receptors on individual inflammatory leukocyte subtypes. Overall, this has previously been interpreted as redundancy and proposed as a protective mechanism to ensure that the inflammatory response is robust. In contrast we have hypothesised that the system is not redundant but exquisitely subtle. Our interests relate to the receptors CCR1, CCR2, CCR3 and CCR5 which, together, regulate non-neutrophilic myeloid cell recruitment to inflammatory sites. Here we demonstrate that, whilst most murine monocytes exclusively express CCR2, there is a small subpopulation, which is expanded during inflammation, which co-expresses CCR1 and CCR2. Combinations of transcript and functional analysis demonstrate that this is not redundant expression and that co-expression of CCR1 and CCR2 marks a phenotypically distinct population of monocytes characterised by expression of genes otherwise typically associated with neutrophils. Single cell RNA sequencing confirms this as a monodisperse population of atypical monocytes. This monocytic population has been previously described as having immunosuppressive activity. Overall, our data confirm combinatorial chemokine receptor expression by a subpopulation of monocytes but demonstrate that this is not redundant expression and marks a discrete monocytic population.
2024-07-10 | GSE251647 | GEO
Project description:CCR1 and CCR2 co-expression on monocytes is nonredundant and delineates a distinct monocyte subpopulation.
| PRJNA1055008 | ENA
Project description:CCR1 and CCR2 co-expression on monocytes is nonredundant and delineates a distinct monocyte subpopulation. [RNA-Seq]
| PRJNA1055013 | ENA
Project description:CCR1 and CCR2 co-expression on monocytes is non-redundant and delineates a distinct monocyte subpopulation. [scRNA-Seq]
| PRJNA1055015 | ENA
Project description:Monocytes and monocyte-derived macrophages facilitate cancer progression and metastasis. Inflammatory monocytes expressing CCR2 are actively recruited to metastatic lungs, where they promote tumor cell extravasation, metastatic outgrowth, and an immunosuppressive environment. The role of CCR1 in this process has remained unclear. We used Ccr1- and Ccr2-deficient mice and two different tumor cells lines, MC38 and LLC1 with and without Ccl2-deficiency in vitro and in vivo. The recruitment of both Ccr1- and Ccr2-deficient monocytes towards the Ccl2 chemokine was significantly impaired, while no substantial recruitment was observed towards Ccl5 in vitro. MC38 and LLC1 Ccl2-deficient tumor cells showed reduced lung metastasis in both Ccr1- and Ccr2-deficient mice when compared to wild-type mice. We detected reduced numbers of macrophages and myeloid cells in both chemokine receptor-deficient mice. Lung metastasis in both Ccr1- and Ccr2-deficient mice could be rescued to the same levels as in wild-type mice by an adoptive transfer of Ccr2-deficient but not Ccr1-deficient monocytic cells. Accumulation of Ccr1-deficient monocytes in the lungs was severely impaired upon intravenous monocyte injection, indicating the importance of this axis in cell recruitment. Moreover, the efficient recruitment of adoptive transferred Ccr2-deficient monocytes to the lungs and the restoration of lung metastasis suggests an involvement of an additional, Ccr2-independent chemokine pathway. This data defines the non-redundant functions of the Ccr1- and Ccr2-chemokine axes in monocyte recruitment and macrophage presence during lung metastasis. While Ccr2 is essential for the release of monocytes from the bone marrow, Ccr1 is primarily responsible for monocyte presence at metastatic sites.
| S-EPMC11617888 | biostudies-literature
Project description:Monocytes undergo phenotypic and functional changes in response to inflammatory cues, but the molecular signals that drive different monocyte states remain largely undefined. We show that monocytes acquire macrophage markers upon glomerulonephritis and may be derived from CCR2+CX3CR1+ double-positive monocytes, which are preferentially recruited, dwell within glomerular capillaries, and acquire proinflammatory characteristics in the nephritic kidney. Mechanistically, the transition to immature macrophages begins within the vasculature and relies on CCR2 in circulating cells and TNFR2 in parenchymal cells, findings that are recapitulated in vitro with monocytes cocultured with TNF-TNFR2-activated endothelial cells generating CCR2 ligands. Single-cell RNA sequencing of cocultures defines a CCR2-dependent monocyte differentiation path associated with the acquisition of immune effector functions and generation of CCR2 ligands. Immature macrophages are detected in the urine of lupus nephritis patients, and their frequency correlates with clinical disease. In conclusion, CCR2-dependent functional specialization of monocytes into macrophages begins within the TNF-TNFR2-activated vasculature and may establish a CCR2-based autocrine, feed-forward loop that amplifies renal inflammation.
| S-EPMC9006314 | biostudies-literature
Project description:Granulocyte-monocyte progenitors (GMPs) and monocyte-dendritic cell progenitors (MDPs) produce monocytes during homeostasis and in response to increased demand during infection. Both progenitor populations are thought to derive from common myeloid progenitors (CMPs), and a hierarchical relationship (CMP-GMP-MDP-monocyte) is presumed to underlie monocyte differentiation. Here, however, we demonstrate that mouse MDPs arose from CMPs independently of GMPs, and that GMPs and MDPs produced monocytes via similar but distinct monocyte-committed progenitors. GMPs and MDPs yielded classical (Ly6Chi) monocytes with gene expression signatures that were defined by their origins and impacted their function. GMPs produced a subset of "neutrophil-like" monocytes, whereas MDPs gave rise to a subset of monocytes that yielded monocyte-derived dendritic cells. GMPs and MDPs were also independently mobilized to produce specific combinations of myeloid cell types following the injection of microbial components. Thus, the balance of GMP and MDP differentiation shapes the myeloid cell repertoire during homeostasis and following infection.
| S-EPMC5726802 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2014-05-02 | E-GEOD-54818 | biostudies-arrayexpress