Reciprocal influence of microbiota composition and TNF alpha inhibitors in spondyloarthritis patients
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB23107 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Reciprocal inlfuence of TNF alpha inhibitor and microbiota composition in spondyloarthritis patients
| PRJEB16329 | ENA
Project description:Reciprocal inlfuence of TNF alpha inhibitor and microbiota composition in spondyloarthritis patients
| PRJEB19186 | ENA
Project description:Objectives: Gut and joint inflammation commonly co-occur in spondyloarthritis (SpA) which strongly restricts therapeutic modalities. The immunobiology underlying differences between gut and joint immune regulation, however, is poorly understood. We therefore assessed the immunoregulatory role of CD4+FOXP3+ regulatory T (Treg) cells in a model of Crohn’s-like ileitis and concomitant arthritis. Methods: RNA-sequencing (RNA-seq) and flow cytometry were performed on inflamed gut and joint samples and tissue-derived Tregs from TNF∆ARE mice. In situ hybridization of TNF and its receptors (TNFR) was applied to human SpA gut biopsies. Soluble(s) TNFR levels were measured in serum of mice and SpA patients and controls. Treg function was explored by in vitro co-cultures and in vivo by conditional Treg depletion. Results: Chronic TNF exposure induced several TNF superfamily (TNFSF) members (4-1BBL, TWEAK and TRAIL) in synovium and ileum in a site-specific manner. Elevated TNFR2 mRNA levels were noted in TNF∆ARE/+ mice leading to increased sTNFR2 release. Likewise, sTNFR2 levels were higher in SpA patients with gut inflammation and distinct from inflammatory and healthy controls. Tregs accumulated at both gut and joints of TNF∆ARE mice, yet their TNFR2 expression and suppressive function was significantly lower in synovium versus ileum. In line herewith, synovial and intestinal Tregs displayed a distinct transcriptional profile with tissue restricted TNFSF receptor and p38MAPK gene expression. Conclusions: These data point to profound differences in immune-regulation between Crohn’s ileitis and peripheral arthritis. Whereas Tregs control ileitis they fail to dampen joint inflammation. Synovial resident Tregs are particularly maladapted to chronic TNF exposure.
2023-05-22 | GSE232406 | GEO
Project description:Objectives: Gut and joint inflammation commonly co-occur in spondyloarthritis (SpA) which strongly restricts therapeutic modalities. The immunobiology underlying differences between gut and joint immune regulation, however, is poorly understood. We therefore assessed the immunoregulatory role of CD4+FOXP3+ regulatory T (Treg) cells in a model of Crohn’s-like ileitis and concomitant arthritis. Methods: RNA-sequencing (RNA-seq) and flow cytometry were performed on inflamed gut and joint samples and tissue-derived Tregs from TNF∆ARE mice. In situ hybridization of TNF and its receptors (TNFR) was applied to human SpA gut biopsies. Soluble(s) TNFR levels were measured in serum of mice and SpA patients and controls. Treg function was explored by in vitro co-cultures and in vivo by conditional Treg depletion. Results: Chronic TNF exposure induced several TNF superfamily (TNFSF) members (4-1BBL, TWEAK and TRAIL) in synovium and ileum in a site-specific manner. Elevated TNFR2 mRNA levels were noted in TNF∆ARE/+ mice leading to increased sTNFR2 release. Likewise, sTNFR2 levels were higher in SpA patients with gut inflammation and distinct from inflammatory and healthy controls. Tregs accumulated at both gut and joints of TNF∆ARE mice, yet their TNFR2 expression and suppressive function was significantly lower in synovium versus ileum. In line herewith, synovial and intestinal Tregs displayed a distinct transcriptional profile with tissue restricted TNFSF receptor and p38MAPK gene expression. Conclusions: These data point to profound differences in immune-regulation between Crohn’s ileitis and peripheral arthritis. Whereas Tregs control ileitis they fail to dampen joint inflammation. Synovial resident Tregs are particularly maladapted to chronic TNF exposure.
2023-05-22 | GSE232405 | GEO
Project description: Not available
| S-EPMC5882885 | biostudies-literature
Project description:Drug serum concentrations will be measured at several time-points for inflammatory disease patients treated with anti-TNF agents. The purpose is to determine which patients that will clinically benefit from either discontinue treatment, adjusting the dose, switch to another anti-TNF agent or a different class of medication.
| 2161631 | ecrin-mdr-crc
Project description:Endothelial-mesenchymal-transition (EndMT) is an important source of cancer-associated fibroblasts (CAFs), which are known to facilitate tumor progression. We have previously shown that EndMT is present in pancreatic tumors and that deficiency of the Tie1 receptor induces EndMT in human endothelial cells. Pancreatic tumors are characterized by the presence of tumor necrosis factor-α (TNF-α). We now show that TNF-α strongly induces human endothelial cells to undergo EndMT. In order to know the secretory feature of cells which undergo EndMT by TNF-α, we conducted a comparative analysis of HMVEC secretome treated or not for 24h and 48h with TNF-α. Secretome study shows that cells treated with TNF-α have an important fibroblast-like secretory capacity, and a proinflamatory signature. Moreover, Ingenuity Pathway Analysis (IPA) shows that pathways implicated in migration, inflammation and fibrosis are predicted to be activated and that necrosis and apoptosis pathways are inhibited. Accordingly cell survival, viability and cycle progression are activated. We show that TNF-α- treated cells secrete proteins related to 16 protumoral pathways, confirming their fibroblastic characteristic. Finally, among the predicted upstream regulators activated, IPA analysis shows that, TNFSF12 and its receptor are present at hight levels in PDAC patients. Altogether these results show the fibroblastic characteristic of treated cells and demonstrate that TNF-α induces CAFs.
2021-09-08 | PXD014488 | Pride
Project description:Association of juvenile spondyloarthritis (jSpA) with the HLA-B27 genotype is well established, but there is little knowledge of other genetic factors with a role in disease development. The aim of the present study was to identify and confirm gene signatures and novel biomarkers in various cohorts of untreated and treated patients diagnosed with jSpA and other forms of juvenile idiopathic arthritis (JIA). DNA microarray gene expression was performed in 11 patients with jSpA and in four healthy controls, along with bioinformatics analysis of retrieved data (DAVID, GSEA, IPA).
2014-10-31 | GSE58667 | GEO
Project description:Association of juvenile spondyloarthritis (jSpA) with the HLA-B27 genotype is well established, but there is little knowledge of other genetic factors with a role in disease development. The aim of the present study was to identify and confirm gene signatures and novel biomarkers in various cohorts of untreated and treated patients diagnosed with jSpA and other forms of juvenile idiopathic arthritis (JIA). DNA microarray gene expression was performed in 11 patients with jSpA and in four healthy controls, along with bioinformatics analysis of retrieved data (DAVID, GSEA, IPA). Total RNA was isolated from whole blood of 45 children with known HLA genotype and diagnosis of jSpA according to ILAR criteria, 11 children with oligo- and polyarticular forms of JIA, as well as 12 age and sex matched control participants without diagnosis of chronic inflammatory disease. Of those 11 patient and 4 controls were utilized in the microarrays experiments, while the rest were used in the follow-up qPCR analyses
2014-10-31 | E-GEOD-58667 | biostudies-arrayexpress
Project description:G-protein coupled receptors (GPCRs) have diverse roles in physiological processes, including immunity. Gs-coupled GPCRs increase while Gi-coupled ones decrease intracellular cAMP. Previous studies suggest that, in epithelial cells, Gs-coupled GPCRs enhance whereas Gi-coupled GPCRs suppress pro-inflammatory immune responses. In order to examine the issue, we chose beta2 adrenergic receptor and GPR40 as representatives of Gs- and Gi- coupled GPCRs, respectively, and examined their effects on TNF-alpha and IFN-gamma-(TNF-alpha + IFN-gamma) induced gene expression by HaCaT. We used microarrays to detail the global changes of gene expression induced by a beta2 adrenergic receptor agonist terbutaline or GPR40 agonist GW9508 pre-treatment in TNF-alpha + IFN-gamma - stimulated HaCaT cells. HaCaT cells were pre-treated with terbutaline or GW9508, TNF-alpha + IFN-gamma were then added, and cultured for another 24 h. Cells were then used for RNA extraction and hybridization on Affymetrix microarrays. We sought to clarify changes in gene expression after 1) TNF-alpha + IFN-gamma, 2) TNF-alpha + IFN-gamma + terbutaline, and 3) TNF-alpha + IFN-gamma + GW9508 treatment. To this end, we set 4 groups of samples; 1) unstimulated group, 2) TNF-alpha + IFN-gamma-stimulated group, 3) TNF-alpha + IFN-gamma + terbutaline-stimulated group, and 4) TNF-alpha + IFN-gamma + GW9508-stimulated group. In each group, HaCaT cells were stimulated in triplicate wells (n=3).
2010-12-01 | E-GEOD-20297 | biostudies-arrayexpress