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Single cell transcriptome and surface protein expression analysis identify OX40+GITR+ pathogenic T helper 17 in anklyosing spondilytis [scRNA-seq]

ABSTRACT: We unveiled the characteristics of pTh17s, which are polyfunctional IL-17A and IFN-γ-producing memory CD4+ T cells. scRNA-seq and cytometry analysis found that the co-expression of OX40 and GITR is increased in pTh17 cells.

ORGANISM(S): Homo sapiens

PROVIDER: GSE216883 | GEO | 2023/02/23

REPOSITORIES: GEO

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Single cell transcriptome and surface protein expression analysis identify OX40+GITR+ pathogenic T helper 17 in anklyosing spondilytis [CITE-seq]

Project description:We unveiled the characteristics of pTh17s, which are polyfunctional IL-17A and IFN-γ-producing memory CD4+ T cells. scRNA-seq and cytometry analysis found that the co-expression of OX40 and GITR is increased in pTh17 cells.

2023-02-23 | GSE216884 | GEO

Analysis of GITR and OX40 signaling complexes

Project description:T cells are pivotal in the adaptive immune defense, necessitating a delicate balance between robust response against infections and self-tolerance. Their activation involves intricate cross-talk among signaling pathways triggered by the T-cell antigen receptors (TCR) and co-stimulatory or inhibitory receptors. The molecular regulation of these complex signaling networks is still incompletely understood. We identified an adaptor protein, ABIN1 as a component of the signaling complexes of GITR and OX40 co-stimulation receptors. T cells lacking ABIN1 exhibit hyper-responsiveness to TCR activation ex vivo, enhanced responses to cognate infections, and superior ability to induce experimental autoimmune diabetes in mice. We observed that ABIN1 negatively regulates NFκB and p38 pathways. The latter was at least partially responsible for the upregulation of key effector proteins, IFNG and GZMB in ABIN1-deficient T cells after TCR stimulation. Our findings reveal the intricate role of ABIN1 in T-cell regulation and its potential as a target for therapeutic fine-tuning T-cell responses.

2024-04-25 | PXD046422 | Pride

Single cell transcriptome and surface protein expression analysis identify OX40+GITR+ pathogenic T helper 17 in anklyosing spondilytis.

Project description:Single cell transcriptome and surface protein expression analysis identify OX40+GITR+ pathogenic T helper 17 in anklyosing spondilytis.

| PRJNA896106 | ENA

Single cell transcriptome and surface protein expression analysis identify OX40+GITR+ pathogenic T helper 17 in anklyosing spondilytis [scRNA-seq]

Project description:Single cell transcriptome and surface protein expression analysis identify OX40+GITR+ pathogenic T helper 17 in anklyosing spondilytis [scRNA-seq]

| PRJNA896111 | ENA

Single cell transcriptome and surface protein expression analysis identify OX40+GITR+ pathogenic T helper 17 in anklyosing spondilytis [CITE-seq]

Project description:Single cell transcriptome and surface protein expression analysis identify OX40+GITR+ pathogenic T helper 17 in anklyosing spondilytis [CITE-seq]

| PRJNA896110 | ENA

GITR and GITRL protects non-epithelioid mesothelioma cells from radiation

Project description:GITR and GITRL overexpress in sarcomatoid mesotelioma cells than epithelioid subtype, and cisplatin or radiation results an increase of GITR and GITRL expression on tumor cells. After sorting CRL9546 cells into GITR+(R), GITRL+(L), and GITR-/GITRL- (DN) cell populations. Three cell subsets were labelled as ligand positive L1, L2, L3, receptor positive R1, R2, R3, and double negative DN1, DN2, DN3. In total: 9 samples. RNA was extracted to run Affymetrix microarray.

2021-11-02 | E-MTAB-10647 | biostudies-arrayexpress

Single cell transcriptome and surface protein expression analysis identify OX40+GITR+ pathogenic T helper 17 in anklyosing spondilytis.

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

2023-02-23 | GSE216885 | GEO

Gene expression analysis of OX40-triggered mouse Treg

Project description:Regulatory T (Treg) maintain the tumor microenvironment in an immunosuppressive state preventing effective anti-tumor immune response. A possible strategy to overcome Treg cell suppression focuses on OX40, a costimulatory molecule expressed constitutively by Treg cells while induced in activated effector T (Teff) cells. OX40 stimulation by the agonist mAb OX86 inhibits Treg cell suppression and boosts Teff cell activation. Here we uncover the mechanisms underlying the therapeutic activity of OX86 treatment dissecting its distinct effects on Treg and on effector memory T (Tem) cells, which are the most abundant CD4+ populations strongly expressing OX40 at the tumor site. In response to OX86, tumor-infiltrating Treg cells produced significantly less interleukin 10 (IL-10), possibly in relation to a decrease in the transcription factor IRF1. Tem cells responded to OX86 by upregulating surface CD40L expression, providing a licensing signal to dendritic cells (DCs). The CD40L/CD40 axis was required for Tem cell-mediated in vitro DC maturation and in vivo DC migration. Accordingly, OX86 treatment was no longer therapeutic in CD40 KO mice. In conclusion, following OX40 stimulation, blockade of Treg cell suppression and enhancement of the Tem cell adjuvant effect both concurred to free DCs from immunosuppression and to activate the immune response against the tumor. Total RNA obtained from sorted mouse FoxP3-GFP+ Treg activated in vitro with anti-CD3 in the presence of an OX40-agonist mAb (OX86) or isotype control.

2011-09-25 | E-GEOD-32373 | biostudies-arrayexpress

Gene expression analysis of Ox40-cre/ROSA-YFP CD4+ T cell subsets

Project description:An Ox40-cre allele was used for lineage marking of CD4 T cells. Naive T cells that had previously expressed OX40 demonstrated a partially activated phenotype that was distinct from that of the majority of naive T cells. These results are consistent with a minor subpopulation of naive T cells being dependent on strong signaling responses to thymic self ligands. Keywords: T cell population comparison. Characterization of a novel subpopulation of naive T cells. Four types of T cells were sorted from mice (naive, CD44lo, CD44hi and Treg).

2010-04-03 | E-GEOD-13502 | biostudies-arrayexpress

Next Generation Sequencing Facilitates Quantitative Analysis of Wild Type APC and OX40L-TG APC induced T helper 17 cell Transcriptomes [RNA-seq]

Project description:Purpose:The goals of this study are to evaluate the effect of OX40 ligation on transcriptome profiling of in vitro polarized T helper 17 cell (RNA-seq). Methods: mRNA profiles of CD4+ T cells cultured in vitro under Th17-polarizing conditions for 48hrs (both Ctrl and OX40L treated groups) were generated by deep sequencing, using Illumina RapidRun. The sequence reads that passed quality filters were analyzed at the transcript isoform level with two methods: Burrows–Wheeler Aligner (BWA) and TopHat followed by CuffDiff. qRT–PCR validation was performed using SYBR Green assays Results: Among the 398 genes that were significantly affected by OX40, only about 11% were previously identified as RORγt target genes in Th17 cells. Conclusions: Our study suggests that OX40 unlikely affects Th17 commitment, but most likely impairs their effector differentiation. As IL-17A and IL-17F are Th17-defining cytokines, their suppression suggests that OX40 may inhibits effector functions of Th17 cells.

2016-10-06 | GSE80010 | GEO

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