RNA-Seq of human lymph node stromal cells during the earliest phases of rheumatoid arthritis
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ABSTRACT:
PROVIDER: PRJEB32277 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR3289160.fastq.gz | Fastqsanger.gz | |||
| ERR3289161.fastq.gz | Fastqsanger.gz | |||
| ERR3289152.fastq.gz | Fastqsanger.gz | |||
| ERR3289162.fastq.gz | Fastqsanger.gz | |||
| ERR3289153.fastq.gz | Fastqsanger.gz |
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Project description:RNA-Seq of human lymph node stromal cells during the earliest phases of rheumatoid arthritis
| PRJEB32277 | ENA
Project description:Lymph node stromal cells (LNSCs) are an important lymphoid tissue cellular type that regulates the immune response and maintain peripheral tolerance. In rheumatoid arthritis, break of tolerance and formation of autoantibodies occurs years before arthritis. Studies in mice have shown lymph nodes activation before the onset of arthritis. We hypothesize that malfunctioning of LNSCs leads to a microenvironment where immune responses are not properly controlled leading to activation of (autoreactive) lymphocytes and the production of autoantibodies. Here we studied human LNSCs and search for differentially expressed genes between RA at risk or RA versus healthy using RNA sequencing in order to identify new therapeutic targets.
2019-07-01 | E-MTAB-7897 | biostudies-arrayexpress
Project description:Lymph node stromal cells (LNSCs) are an important lymphoid tissue cellular type that regulates the immune response and maintain peripheral tolerance. In rheumatoid arthritis, break of tolerance and formation of autoantibodies occurs years before arthritis. Studies in mice have shown lymph nodes activation before the onset of arthritis. We hypothesize that malfunctioning of LNSCs leads to a microenvironment where immune responses are not properly controlled leading to activation of (autoreactive) lymphocytes and the production of autoantibodies. Here we studied human LNSCs and search for differentially methylated genes between RA versus healthy using Illumina human methylation arrays in order to identify new epigenetic targets.
2019-07-01 | E-MTAB-8085 | biostudies-arrayexpress
Project description:BACKGROUND:Systemic autoimmunity can be present years before clinical onset of rheumatoid arthritis (RA). Adaptive immunity is initiated in lymphoid tissue where lymph node stromal cells (LNSCs) regulate immune responses through their intimate connection with leucocytes. We postulate that malfunctioning of LNSCs creates a microenvironment in which normal immune responses are not properly controlled, possibly leading to autoimmune disease. In this study we established an experimental model for studying the functional capacities of human LNSCs during RA development. METHODS:Twenty-four patients with RA, 23 individuals positive for autoantibodies but without clinical disease (RA risk group) and 14 seronegative healthy control subjects underwent ultrasound-guided inguinal lymph node (LN) biopsy. Human LNSCs were isolated and expanded in vitro for functional analyses. In analogous co-cultures consisting of LNSCs and peripheral blood mononuclear cells, ?CD3/?CD28-induced T-cell proliferation was measured using carboxyfluorescein diacetate succinimidyl ester dilution. RESULTS:Fibroblast-like cells expanded from the LN biopsy comprised of fibroblastic reticular cells (gp38+CD31-) and double-negative (gp38-CD31-) cells. Cultured LNSCs stably expressed characteristic adhesion molecules and cytokines. Basal expression of C-X-C motif chemokine ligand 12 (CXCL12) was lower in LNSCs from RA risk individuals than in those from healthy control subjects. Key LN chemokines C-C motif chemokine ligand (CCL19), CCL21 and CXCL13 were induced in LNSCs upon stimulation with tumour necrosis factor-? and lymphotoxin ?1?2, but to a lesser extent in LNSCs from patients with RA. The effect of human LNSCs on T-cell proliferation was ratio-dependent and altered in RA LNSCs. CONCLUSIONS:Overall, we developed an experimental model to facilitate research on the role of LNSCs during the earliest phases of RA. Using this innovative model, we show, for the first time to our knowledge, that the LN stromal environment is changed during the earliest phases of RA, probably contributing to deregulated immune responses early in disease pathogenesis.
| S-EPMC5828373 | biostudies-literature
Project description:Rheumatoid arthritis (RA) is a progressive, destructive autoimmune arthritis. Break of tolerance and formation of autoantibodies occur years before arthritis. Adaptive immunity is initiated in lymphoid tissue where lymph node stromal cells (LNSCs) play a crucial role in shaping the immune response and maintaining peripheral tolerance. Here we performed the first epigenomic characterization of LNSCs during health and early RA, by analyzing their transcriptome and DNA methylome in LNSCs isolated from lymph node needle biopsies obtained from healthy controls (HC), autoantibody positive RA-risk individuals and patients with established RA. Of interest, LNSCs from RA-risk individuals and RA patients revealed a common significantly differential expressed gene signature compared with HC LNSCs. Pathway analysis of this common signature showed, among others, significant enrichment of pathways affecting the extracellular matrix (ECM), cholesterol biosynthesis and immune system. In a gel contraction assay LNSCs from RA-risk individuals and RA patients showed impaired collagen contraction compared to healthy LNSCs. In RA LNSCs a significant enrichment was observed for genes involved in cytokine signaling, hemostasis and packaging of telomere ends. In contrast, in RA-risk LNSCs pathways in cancer (cell cycle related genes) were differentially expressed compared with HC, which could be validated in vitro using a proliferation assay, which indicated a slower proliferation rate. DNA methylation analyses revealed common and specific differentially methylated CpG sites (DMS) in LNSC from RA patients and RA-risk individuals compared with HC. Intriguingly, shared DMS were all associated with antigen processing and presentation. This data point toward alterations in cytoskeleton and antigen-processing and presentation in LNSC from RA-risk individuals and RA patients. Further studies are required to investigate the consequence of this LNSC abnormality on LNSC-mediated immunomodulation.
| S-EPMC6711342 | biostudies-literature
Project description:Rheumatoid arthritis (RA) is a chronic, inflammatory joint disease of unknown etiology and pronounced inter-patient heterogeneity. To characterize RA at the molecular level and to uncover key pathomechanisms, we performed whole-genome gene expression analyses. Synovial tissues from rheumatoid arthritis patients were compared to those from osteoarthritis patients and to normal donors. Keywords: disease state analysis
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Project description:RNA-Seq of human lymph node stromal cells during the earliest phases of rheumatoid arthritis
2019-08-05 | E-MTAB-7897 | ExpressionAtlas
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2018-03-19 | GSE110008 | GEO