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CCR1 and CCR2 co-expression on monocytes is non-redundant and delineates a distinct monocyte subpopulation. [scRNA-Seq]

ABSTRACT: CCR1 and CCR2 co-expression on monocytes is non-redundant and delineates a distinct monocyte subpopulation. [scRNA-Seq]

PROVIDER: PRJNA1055015 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR27295924_1.fastq.gz	Fastqsanger.gz
	SRR27295924_2.fastq.gz	Fastqsanger.gz

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CCR1 and CCR2 co-expression on monocytes is non-redundant and delineates a distinct monocyte subpopulation. [scRNA-Seq]

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.

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CCR1 and CCR2 co-expression on monocytes is nonredundant and delineates a distinct monocyte subpopulation. [RNA-Seq]

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CCR1 and CCR2 co-expression on monocytes is nonredundant and delineates a distinct monocyte subpopulation.

Project description:CCR1 and CCR2 co-expression on monocytes is nonredundant and delineates a distinct monocyte subpopulation.

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CCR1 and CCR2 co-expression on monocytes is nonredundant and delineates a distinct monocyte subpopulation. [RNA-Seq]

Project description:CCR1 and CCR2 co-expression on monocytes is nonredundant and delineates a distinct monocyte subpopulation. [RNA-Seq]

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CCR1 and CCR2 Coexpression on Monocytes Is Nonredundant and Delineates a Distinct Monocyte Subpopulation.

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CCR1 and CCR2 co-expression on monocytes is nonredundant and delineates a distinct monocyte subpopulation.

Project description:This SuperSeries is composed of the SubSeries listed below.

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Transcriptome comparison between CCR2+ and CCR2- classical monocytes in SIV-infected Macaca nemestrina

Project description:Monocytes have been categorized in three main subpopulations based on CD14 and CD16 surface expression. Classical monocytes are the most abundant subset in the blood. They express a CD14+CD16-CCR2+ phenotype, which confers on them the ability to migrate to inflammatory sites by quickly responding to CCL2 signaling. Here we identified and characterized the surge and expansion of a novel monocyte subset during SIV and HIV infection. They were undistinguishable from classical monocytes regarding CD14 and CD16 expression, but did not express surface CCR2. Transcriptome analysis of sorted cells confirmed that they represent a distinct subpopulation that expresses lower levels of inflammatory cytokines and activation markers than their CCR2+ counterparts. They exhibited impaired phagocytosis and deficient chemotaxis in response to CCL2 and CCL7, besides being refractory to SIV infection. We named these cells atypical CCR2- classical (ACC) monocytes, and believe they play an important role in AIDS pathogenesis, possibly reflecting an anti-inflammatory response against the extreme immune activation observed during SIV and HIV infection. Antiretroviral therapy caused this population to decline in both macaque and human subjects, suggesting that this atypical phenotype may be induced by viral replication. Expression profiling by NanoString nCounter gene expression system. Classical monocytes (CD14++CD16-) from six SIV-infected macaques (day 14 post inoculation) were sorted in two groups according to CCR2 expression.

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