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TNF plays a crucial role in inflammation by signaling via T cell TNFR2 [scRNA-seq]

ABSTRACT: Identification of differentially expressed genes between WT and Tnfr2-/- CD4+ T cells in Experimental autoimmune encephalomyelitis (EAE).

ORGANISM(S): Mus musculus

PROVIDER: GSE188161 | GEO | 2021/11/06

REPOSITORIES: GEO

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TNFR2 is critical for TNF-induced rheumatoid arthritis fibroblast-like synoviocyte inflammation

Project description:Objectives: TNF-induced activation of fibroblast-like synoviocytes (FLS) is a critical determinant for synovial inflammation and joint destruction in rheumatoid arthritis (RA). The detrimental role of TNF-receptor 1 (TNFR1) has thoroughly been characterized. The contributions of TNFR2, however, are largely unknown. This study was performed to delineate the role of TNFR2 in human FLS activation. Methods: TNFR2 expression in synovial tissue samples was determined by immunohistochemistry. Expression of TNFR2 was silenced using RNAi or CRISPR/Cas9 technologies. Global transcriptional changes were determined by RNA-seq. QPCR, ELISA and immunoblotting were used to validate RNA-seq results and to uncover pathways operating downstream of TNFR2 in FLS. Results. TNFR2 expression was increased in RA when compared to OA synovial tissues. In particular, RA-FLS demonstrated higher levels of TNFR2 when compared to OA-FLS. TNFR2 expression in RA-FLS correlated with RA disease activity, synovial T- and B-cell infiltration. TNF and IL1 were identified as inflammatory mediators that upregulate TNFR2 in RA-FLS. Silencing of TNFR2 in RA-FLS markedly diminished the TNF-induced expression of inflammatory cytokines and chemokines, including CXCR3-binding chemokines and the B-cell activating factor TNFSF13B. Immunobiochemical analyses revealed that TNFR2-mediated expression of inflammatory mediators critically depends on STAT1. Conclusion: Our results define a critical role for TNFR2 in FLS-driven inflammation and unfold its participation in the unresolved course of synovial inflammation in RA.

2022-04-26 | GSE195557 | GEO

TNF plays a crucial role in inflammation by signaling via T cell TNFR2 [scRNA-seq]

Project description:TNF plays a crucial role in inflammation by signaling via T cell TNFR2 [scRNA-seq]

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TNF plays a crucial role in inflammation by signaling via T cell TNFR2

Project description:TNF plays a crucial role in inflammation by signaling via T cell TNFR2

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Opposite functions of microglial and macrophagial TNFR2 in EAE pathogenesis: the good versus the bad.

Project description:In MS pathophysiology, soluble tumor necrosis factor (TNF) has been attributed detrimental functions, whereas transmembrane TNF promotes neurorepair primarily by activating TNF receptor 2 (TNFR2). Here we investigate the role of TNFR2 in microglia and peripheral monocyte/macrophages in EAE using novel cell-specific conditional knockouts. We show that microglial TNFR2 ablation leads to early onset of EAE, with increased CNS leucocyte infiltration, T cell activation, and demyelination. TNFR2-ablated microglia shows a more pro-inflammatory phenotype, with dysregulation of genes controlling innate immunity and host defense. Conversely, monocyte/macrophagial TNFR2 ablation results in EAE suppression, with impaired peripheral T cell activation. Our work uncovers a dichotomy of function for TNFR2 in myeloid cells, with microglial TNFR2 providing protective signals to contain disease, and monocyte/macrophagial TNFR2 driving immune activation and EAE initiation. This needs to be taken into account when targeting TNFR2 for therapeutic purposes in neuroinflammatory diseases to which both populations are key contributors.

2016-11-21 | GSE78082 | GEO

TNF plays a crucial role in inflammation by signaling via T cell TNFR2

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

2021-11-06 | GSE188162 | GEO

TNF plays a crucial role in inflammation by signaling via T cell TNFR2 [bulkRNA-seq]

Project description:TNF plays a crucial role in inflammation by signaling via T cell TNFR2 [bulkRNA-seq]

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TNF plays a crucial role in inflammation by signaling via T cell TNFR2 [bulkRNA-seq]

Project description:TNF regulates the inflammatory cytokine secretion from CD4+ T cells in vitro.

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Apelin 13 breaks the immune cell route from lung to brain [scRNA-Seq]

Project description:To investigate the effect of Apelin 13 on lung in experimental autoimmune encephalomyelitis(EAE) at peak, we perform single cell RNA sequencing of the whole lung of Control, EAECont and EAE with Apelin 13 treatment(EAEA13)

2024-06-14 | GSE230550 | GEO

Proteomic analysis in multiple sclerosis

Project description:To address the differential response of the CNS, proteomics was applied in experimental autoimmune encephalomyelitis (EAE) mice and cuprizone (CPZ) mice in two different CNS regions

2023-09-27 | PXD037019 | JPOST Repository

Comparative genomic hybridization of experimental autoimmune encephalomyelitis (EAE)-susceptible DA and EAE-resistant PVG rat strains stimulated with myelin oligodendrocyte glycoprotein (MOG) to identify the alternative splicing.

Project description:Experimental autoimmune encephalomyelitis (EAE)-susceptible DA and EAE-resistant PVG rats were immunized with myelin oligodendrocyte glycoprotein (MOG) to induce an autoimmune response.<br>Seven days later draining inguinal lymph nodes were removed. 2 conditions were examined: 'ex vivo' and 'MOG restimulated', which involved 24hrs of incubation with an encephalogenic MOG 91-108 peptide.

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