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Bone marrow-derived macrophages from a murine model of Sjögren's syndrome demonstrate an aberrant, inflammatory response to apoptotic cells

ABSTRACT: Bone marrow-derived macrophages from a murine model of Sjögren's syndrome demonstrate an aberrant, inflammatory response to apoptotic cells

PROVIDER: PRJNA780011 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR16936780_1.fastq.gz	Fastqsanger.gz
	SRR16936780_2.fastq.gz	Fastqsanger.gz
	SRR16936781_1.fastq.gz	Fastqsanger.gz
	SRR16936781_2.fastq.gz	Fastqsanger.gz
	SRR16936782_1.fastq.gz	Fastqsanger.gz

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Bone marrow-derived macrophages from a murine model of Sjögren's syndrome demonstrate an aberrant, inflammatory response to apoptotic cells

Project description:We report that bone marrow derived macrophages from our Sjögren's syndrome mouse model exhibit an elevated inflammatory response to both apoptotic cells and TLR stimuli according to RNA-Seq data and pathway anyalysis

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Bone marrow-derived macrophages from a murine model of Sjogren's syndrome demonstrate an aberrant, inflammatory response to apoptotic cells.

Project description:Sjögren's syndrome (SjS) is a female-dominated autoimmune disease involving lymphocytic infiltration of the exocrine glands. We have previously demonstrated cleavage of the TAM (Tyro3, Axl, Mer) receptor Mer is enhanced in SjS, leading to defective efferocytosis. Mer also plays a role in modulating phagocyte inflammatory response to apoptotic cells. Here we investigated the SjS macrophage response to apoptotic cells (AC). Bone marrow-derived macrophages (BMDMs) from SjS-susceptible (SjSs) C57BL/6.NOD-Aec1Aec2 mice and C57BL/6 (B6) controls were treated with either AC or CpG-oligodeoxynucleotides. RNA was collected from macrophages and bulk sequencing was performed to analyze transcripts. Cytokine expression was confirmed by Bio-plex. RT-qPCR was used to determine toll-like receptor (TLR) 7 and 9 involvement in BMDM inflammatory response to apoptotic cells. SjSS BMDMs exhibited a distinct transcriptional profile involving upregulation of a broad array of inflammatory genes that were not elevated in B6 BMDMs by AC. Inhibition of TLR 7 and 9 was found to limit the inflammatory response of SjSS BMDMs to ACs. ACs elicit an inflammatory reaction in SjSS BMDMs distinct from that observed in B6 BMDMs. This discovery of aberrant macrophage behavior in SjS in conjunction with previously described efferocytosis defects suggests an expanded role for macrophages in SjS, where uncleared dead cells stimulate an inflammatory response through macrophage TLRs recruiting lymphocytes, participating in co-stimulation and establishing an environment conducive to autoimmunity.

| S-EPMC9124194 | biostudies-literature

Whole-Blood gene expression profiling in primary Sjögren's Syndrome and healthy controls

Project description:Investigating differential gene expression between clinical phenotypes in primary Sjögren's Syndrome using matched healthy controls as a further comparator group. Samples are derived from the UK Primary Sjögren's Syndrome Registry (UKPSSR)

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Hypomethylation mediates genetic association with the major histocompatibility complex genes in Sjögren's syndrome

Project description:A causal mediation analysis of DNA methylation as a mediator of nearby genetic association with Sjögren's syndrome using data collected from 131 female members of the Sjögren's International Collaborative Clinical Alliance registry, comprising of 64 Sjögren's syndrome cases and 67 non-cases.

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PBMCs from patients with Sjögren's syndrome and healthy controls

Project description:Sjögren's syndrome is an autoimmune disease manifesting primarily as dryness of eyes and mouth. In this study, we compared gene expression in PBMCs between age- and gender-matched patients with Sjögren's syndrome (diagnosed by ACR criteria) and healthy controls. Cells were collected in heparinized tubes and PBMCs were prepared using Ficoll.

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Epigenetic Signatures of Salivary Gland Inflammation in Sjögren's Syndrome.

Project description:Genome wide DNA methylation profiling of human labial salivary gland (LSG) biopsy samples obtained from 28 female members of the Sjögren's International Collaborative Clinical Alliance (SICCA) Registry. The Illumina HumanMethylation450 BeadChip platform was used to obtain DNA methylation profiles across more than 450,000 highly informative CpG sites. Samples included 15 non-case glands, and 13 glands from patients with Sjögren's Syndrome.

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Project description:Apoptosis accounts for ~ 90% of homeostatic cell turnover in the body1. While caspase-dependent apoptosis is known to influence immune tolerance, induction of cell proliferation, and tissue regeneration2-4, how these apoptotic cells contribute to such diverse effects is less understood. Soluble factors released from apoptotic cells could be a means of ‘talking’ to healthy cells in the tissue neighborhood. While a few phagocyte-attracting ‘find-me’ signals released from apoptotic cells are known5, the larger ‘metabolite secretome’ from apoptotic cells is not yet defined. Here, via unbiased profiling of the apoptotic cell secretome, we identified 123 metabolites that are specifically released during apoptosis, while cells still retain membrane integrity. Release of ~25 of these metabolites is dependent on Pannexin 1 (Panx1) channels, which are opened by caspase-dependent cleavage during apoptosis. Interestingly, one of the Panx1-dependent metabolites from apoptotic cells is spermidine, a polyamine whose release could be, in part, due to the continued metabolic activity of dying cells. RNAseq analysis of healthy cells exposed to the apoptotic secretome revealed Panx1-dependent gene programs, including genes linked to suppression of inflammation, cell proliferation, and wound healing. Analysis of the apoptotic secretome across cell types and different apoptotic stimuli, identified a core “set” of 8 Panx1-dependent metabolites. Strikingly, a selected cocktail of these metabolites demonstrated significant immunosuppressive effects by potently reducing disease severity in an inflammatory arthritis model and a lung graft rejection model. Collectively, these data advance the concept that apoptotic cells are not ‘inert’ corpses waiting for removal by phagocytes, but rather they actively communicate with the tissue environment through their metabolite secretome, with implications in tissue inflammation.

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Ribosome profiling and mRNA seq demonstrate that insertion of common resistance cassettes in yeast drives aberrant transcription

Project description:Ribosome profiling and mRNA seq demonstrate that insertion of common resistance cassettes in yeast drives aberrant transcription

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Transcriptome data of B cells in patients with primary Sjögren's syndrome

Project description:We compared subsets of B cells as follows: Bm1 cells; CD38-IgD+, naïve B cells; CD38+IgD+, pre-germinal centre B cells; CD38highIgD+ and memory B cells; CD38±IgD that were collected from patients with primary Sjögren's syndrome. As a result, list of 623 differentially expressed genes was created. We found interferon signature genes and HLA genes were mostly up-regulated in patients compared to healthy controls.

2019-09-03 | GSE135809 | GEO

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