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Distinct immune modulatory roles of regulatory T cells in gut versus joint inflammation in TNF driven spondyloarthritis

ABSTRACT: Distinct immune modulatory roles of regulatory T cells in gut versus joint inflammation in TNF driven spondyloarthritis

PROVIDER: PRJNA971937 | ENA |

REPOSITORIES: ENA

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Distinct immune modulatory roles of regulatory T cells in gut versus joint inflammation in TNF driven spondyloarthritis [II]

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

Distinct immune modulatory roles of regulatory T cells in gut versus joint inflammation in TNF driven spondyloarthritis [I]

2023-05-22 | GSE232405 | GEO

Distinct immune modulatory roles of regulatory T cells in gut versus joint inflammation in TNF driven spondyloarthritis [II]

Project description:Distinct immune modulatory roles of regulatory T cells in gut versus joint inflammation in TNF driven spondyloarthritis [II]

| PRJNA971943 | ENA

Distinct immune modulatory roles of regulatory T cells in gut versus joint inflammation in TNF driven spondyloarthritis [I]

Project description:Distinct immune modulatory roles of regulatory T cells in gut versus joint inflammation in TNF driven spondyloarthritis [I]

| PRJNA971941 | ENA

Distinct immune modulatory roles of regulatory T cells in gut versus joint inflammation in TNF driven spondyloarthritis

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

2023-05-22 | GSE232407 | GEO

Metagenomic Spondyloarthritis

Project description:Reciprocal inlfuence of TNF alpha inhibitor and microbiota composition in spondyloarthritis patients

| PRJEB19186 | ENA

Reciprocal influence of microbiota composition and TNF alpha inhibitors in spondyloarthritis patients

Project description:Reciprocal influence of microbiota composition and TNF alpha inhibitors in spondyloarthritis patients

| PRJEB23107 | ENA

microbiota composition in spondyloarthritis

Project description:Reciprocal inlfuence of TNF alpha inhibitor and microbiota composition in spondyloarthritis patients

| PRJEB16329 | ENA

Levofloxacin induces the downexpression of inflammation-related transcriptome in the tarsal joint of Spondyloarthritis DBA/1 mice.

Project description:Levofloxacin induces the downexpression of inflammation-related transcriptome in the tarsal joint of Spondyloarthritis DBA/1 mice.

| PRJNA892513 | ENA

Proteomics analysis of plasma from radiographic axial spondyloarthritis patients.

Project description:Tandem mass spectrometry analysis of proteins from depleted plasma from radiographic axial spondyloarthritis patients pre- and post-treated with adalimumab.

2024-05-02 | PXD026189 | Pride

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