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FOXP3 protects conventional human T cells from premature restimulation-induced cell death

ABSTRACT: FOXP3 protects conventional human T cells from premature restimulation-induced cell death

PROVIDER: PRJNA575256 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR10212106_1.fastq.gz	Fastqsanger.gz
	SRR10212106_2.fastq.gz	Fastqsanger.gz
	SRR10212107_1.fastq.gz	Fastqsanger.gz
	SRR10212107_2.fastq.gz	Fastqsanger.gz
	SRR10212108_1.fastq.gz	Fastqsanger.gz

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Similar Datasets

FOXP3 protects conventional human T cells from premature restimulation-induced cell death

Project description:Transcriptome profiling and functional analyses on expanding Tcons revealed that FOXP3 enhances expression of the SLAM family receptor CD48, which in turn sustains basal autophagy and suppresses pro-apoptotic p53 signaling. Our findings suggest that FOXP3 governs a distinct transcriptional program in early-stage effector Tcons that maintains RICD resistance via CD48-dependent protective autophagy and p53 suppression.

2019-12-15 | GSE138272 | GEO

FOXP3 protects conventional human T cells from premature restimulation-induced cell death.

Project description:The adaptive immune response relies on specific apoptotic programs to maintain homeostasis. Conventional effector T cell (Tcon) expansion is constrained by both forkhead box P3 (FOXP3)+-regulatory T cells (Tregs) and restimulation-induced cell death (RICD), a propriocidal apoptosis pathway triggered by repeated stimulation through the T-cell receptor (TCR). Constitutive FOXP3 expression protects Tregs from RICD by suppressing SLAM-associated protein (SAP), a key adaptor protein that amplifies TCR signaling strength. The role of transient FOXP3 induction in activated human CD4 and CD8 Tcons remains unresolved, but its expression is inversely correlated with acquired RICD sensitivity. Here, we describe a novel role for FOXP3 in protecting human Tcons from premature RICD during expansion. Unlike FOXP3-mediated protection from RICD in Tregs, FOXP3 protects Tcons through a distinct mechanism requiring de novo transcription that does not require SAP suppression. Transcriptome profiling and functional analyses of expanding Tcons revealed that FOXP3 enhances expression of the SLAM family receptor CD48, which in turn sustains basal autophagy and suppresses pro-apoptotic p53 signaling. Both CD48 and FOXP3 expression reduced p53 accumulation upon TCR restimulation. Furthermore, silencing FOXP3 expression or blocking CD48 decreased the mitochondrial membrane potential in expanding Tcons with a concomitant reduction in basal autophagy. Our findings suggest that FOXP3 governs a distinct transcriptional program in early-stage effector Tcons that maintains RICD resistance via CD48-dependent protective autophagy and p53 suppression.

| S-EPMC7852538 | biostudies-literature

CD48-dependent protective autophagy in conventional human T cells promotes restimulation-induced cell death resistance

Project description:CD48-dependent protective autophagy in conventional human T cells promotes restimulation-induced cell death resistance

| PRJNA573899 | ENA

Comparative proteomic analysis of mouse CD4+Foxp3+ regulatory T cells and CD4+Foxp3- conventional T cells

Project description:In this study, we compared the proteomes of mouse CD4+Foxp3+ regulatory T cells (Treg) and CD4+Foxp3- conventional T cells (Tconv) in order to build a data set of proteins differentially regulated in these two cell populations. The data set contains mass spectrometry results from the analysis of 7 biological replicates of Treg/Tconv cell samples purified by flow cytometry, each experiment performed from a pool of 4-5 mice. Global proteomic analysis of each sample was performed by single-run nanoLC-MS/MS, using chromatographic separation of peptides on 50cm C18 reverse-phase columns, with either a 480min gradient on LTQ-Velos orbitrap mass spectrometer (replicates 1 and 2) or a 300min gradient on Q-Exactive orbitrap mass spectrometer (replicates 3-7). Several MS injection replicates were performed for some experiments, leading to 27 raw files composing the data set. The detailed description of each analysis (file name, sample type, biological replicate number, MS technical replicate number, MS instrument used, sample name in MaxQuant ouput) is given in the table “Files list.txt”.

2017-04-10 | PXD004436 | Pride

Differentiation of T-regulatory type 1 cells into an immunoregulatory Foxp3+ subset distinct from conventional FoxP3+ T-regulatory cells

Project description:T-regulatory type-1 (TR1) cells are a subset of interleukin-10-producing but FoxP3-negative Treg cells that arise in vivo in response to chronic antigenic stimulation. We have shown that repetitive systemic delivery of autoimmune disease-relevant peptide-major histocompatibility complex class II (pMHCII)-coated nanoparticles (pMHCII-NP) triggers the formation of large pools of disease-suppressing Foxp3– TR1 cells from cognate T-follicular helper (TFH) cell precursors. Here we show that these Foxp3– TR1 cells spontaneously differentiate into a novel immunoregulatory Foxp3+ TR1 subset that inherits transcriptional and epigenetic hallmarks of their precursors and is distinct from other Foxp3+ Treg cell subsets described to date. Development of this novel Foxp3+ Treg cell subset, as is also the case for Foxp3– TR1 cells but not conventional Foxp3+ Treg cells, is BLIMP1-dependent. In a model of central nervous system autoimmunity, deletion of Il10 in the Foxp3+ TR1 subset, but not its FoxP3+ counterpart, reduces the therapeutic activity of pMHCII-NPs without impairing their pharmacodynamic activity. T cell-specific deletion of Prdm1 and deletion of Il10 in both the FoxP3– and FoxP3+ TR1 subsets almost completely abrogate the therapeutic activity of these compounds. Thus, the TFH-TR1 transdifferentiation pathway evolves through 4 distinct cellular states that culminate in the generation of IL-10-producing FoxP3– and FoxP3+ TR1 subsets in a BLIMP1-dependent manner. This transdifferentiation pathway represents a new target for therapeutic intervention in immunity and autoimmunity.

2025-02-26 | GSE252235 | GEO

RNA-seq of FOXP3+ CD4SP regulatory T cells and their FOXP3- CD4SP conventional counterparts from the human thymus

Project description:RNA-seq of FOXP3+ CD4SP regulatory T cells and their FOXP3- CD4SP conventional counterparts from the human thymus

| PRJEB49090 | ENA

ATAC-seq of FOXP3+ CD4SP regulatory T cells and their FOXP3- CD4SP conventional counterparts from the human thymus

Project description:ATAC-seq of FOXP3+ CD4SP regulatory T cells and their FOXP3- CD4SP conventional counterparts from the human thymus

| PRJEB49131 | ENA

RNA-seq of FOXP3+ CD4+ regulatory T cells and their FOXP3- CD4+ conventional counterparts from human peripheral blood

Project description:RNA-seq of FOXP3+ CD4+ regulatory T cells and their FOXP3- CD4+ conventional counterparts from human peripheral blood

| PRJEB74064 | ENA

Inverted chromatin immunoprecipitation identifies Tcf1 as a negative regulator of Foxp3 expression

Project description:Regulatory T (Treg) cells are important regulators of the immune system and have versatile functions for the homeostasis and repair of tissues. They express the forkhead box transcription factor Foxp3 as a lineage-defining protein. In mature Treg cells, the Foxp3 core promoter is unmethylated indicating that this area could harbor a transcription factor complex to initiate or repress gene expression, respectively. We used an unbiased method to identify Foxp3-promoter-binding transcription factors (TFs) by inverted chromatin immunoprecipitation (IP) followed by quantitative mass spectrometry. We identified several candidate factors which showed Foxp3-promoter suppressive capacity, one of which was T-cell factor 1 (Tcf1). Using viral overexpression and CRISPR/Cas knockout studies, we identified Tcf1 as a repressor of Foxp3 expression in primary conventional CD4 T cells (Tconv). In Tcf1-deficient animals, increased levels of Foxp3intermediateCD25negative T cells were identified in secondary lymphoid tissues, implicating that Tcf1 protects Foxp3-negative T cells from inadvertent Foxp3 expression.

2020-05-26 | PXD018764 | Pride

The DEL-1–β3 integrin axis promotes Runx-1–dependent Foxp3 expression and regulatory T cell responses at mucosal barrier sites

Project description:Foxp3+CD4+ regulatory T cells (Tregs) are critical for immune homeostasis and respond to local tissue cues, which control their stability and function. We explored here whether DEL-1, which, like Tregs, increases during resolution of inflammation, promotes Treg responses. DEL-1 enhanced Treg numbers and function at barrier sites (oral and lung mucosa). The underlying mechanism was dissected using mice lacking DEL-1 or expressing a point mutant thereof, or mice with CD4-specific deletion of the transcription factor Runx1, identified by RNA-seq analysis of the DEL-1-induced Treg transcriptome. Specifically, through interaction with avβ3-integrin, DEL-1 promoted induction of Runx1-dependent Foxp3 expression and conferred stability of Foxp3 expression upon Treg restimulation in the absence of exogenous TGFβ1. Additionally, DEL-1 increased RUNX1 and FOXP3 expression in human conventional T cells promoting their conversion into induced Tregs with increased TSDR demethylation, increased stability and suppressive activity. We thus uncovered a DEL-1-avβ3-Runx1 axis that promotes Treg responses at barrier sites and offers novel therapeutic options for modulating inflammatory/autoimmune disorders.

2020-12-31 | GSE131315 | GEO

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