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Locally renewing resident synovial macrophages provide a protective barrier for the joint

ABSTRACT: Locally renewing resident synovial macrophages provide a protective barrier for the joint

PROVIDER: PRJNA556088 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR9684070.fastq.gz	Fastqsanger.gz
	SRR9684071.fastq.gz	Fastqsanger.gz
	SRR9684072.fastq.gz	Fastqsanger.gz
	SRR9684073.fastq.gz	Fastqsanger.gz
	SRR9684074.fastq.gz	Fastqsanger.gz

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Locally renewing resident synovial macrophages provide a protective barrier for the joint [RNA-seq]

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Locally renewing resident synovial macrophages provide a protective barrier for the joint [scRNA-seq]

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

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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.

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Locally renewing resident synovial macrophages provide a protective barrier for the joint

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