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Molecular reframing of fibroblasts during resolution of arthritis [RNA]

ABSTRACT: Molecular reframing of fibroblasts during resolution of arthritis [RNA]

PROVIDER: PRJNA952240 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR24066477_1.fastq.gz	Fastqsanger.gz
	SRR24066477_2.fastq.gz	Fastqsanger.gz
	SRR24066478_1.fastq.gz	Fastqsanger.gz
	SRR24066478_2.fastq.gz	Fastqsanger.gz
	SRR24066479_1.fastq.gz	Fastqsanger.gz

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Molecular reframing of fibroblasts during resolution of arthritis

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Molecular reframing of fibroblasts during resolution of arthritis [scRNA]

Project description:Fibroblasts are key orchestrators of inflammation. Little is known whether these cells change phenotype during resolution of inflammation. We adopted a method to visualise fibroblast activation during inflammation in humans in vivo, which is based on a fibroblast activation protein (FAP) tracer detected by positron emission tomography (PET). While tracer accumulation was high in active arthritis, it decreased significantly after TNF- and IL-17A inhibition. Biopsy-based scRNA-seq analyses in experimental arthritis demonstrated that FAP signal reduction reflected a phenotypic switch from pro-inflammatory MMP3+/IL6+ fibroblasts (high FAP internalisation) to pro-resolving CD200+DKK3+ fibroblasts (low FAP internalisation). Spatial transcriptomics of human joints revealed that pro-resolving niches of CD200+DKK3+ fibroblasts clustered with innate lymphoid cells (ILC)2, whereas MMP3+/IL6+ fibroblasts were co-localised with inflammatory immune cells. CD200+DKK3+ fibroblasts stabilised the ILC2 phenotype and induced resolution of arthritis via CD200/CD200R1 pathway. Taken together, these data suggest a dynamic molecular regulation of the mesenchymal compartment during resolution of inflammation.

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Molecular reframing of fibroblasts during resolution of arthritis

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

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Sequencing of synovial tissue fibroblasts from Rheumatoid Arthritis patients that were co-cultured with inflammatory macrophages.

Project description:The role of synovial tissue fibroblasts and macrophages interactions in driving chronic inflammation and resolution of arthritis is unknown. In this project, we used bulk RNAseq to investigate the impact of different phenotypes of macrophages on activation of synovial fibroblasts.

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