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STAT4 increases the phenotypic and functional heterogeneity of tissue-resident memory T cells

ABSTRACT: STAT4 increases the phenotypic and functional heterogeneity of tissue-resident memory T cells

PROVIDER: PRJNA769589 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR16248414_1.fastq.gz	Fastqsanger.gz
	SRR16248414_2.fastq.gz	Fastqsanger.gz
	SRR16248415_1.fastq.gz	Fastqsanger.gz
	SRR16248415_2.fastq.gz	Fastqsanger.gz
	SRR16248416_1.fastq.gz	Fastqsanger.gz

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STAT4 increases the phenotypic and functional heterogeneity of tissue-resident memory T cells

Project description:We identified STAT4 as a regulator of tissue-resident memory T cell differentiation after infection. Single cell RNA sequencing was used to define the heterogeneity in gene expression among T cells in the lamina proprian and more clearly identify populations that are lost in a STAT4-deficient setting.

2023-04-05 | GSE185545 | GEO

Transcriptional and phenotypic profile of lung-resident memory B cells induced by influenza infection

Project description:Long-lived, tissue-resident memory B cells (BRM) are established in the lungs of mice after pulmonary influenza infection. Influenza-specific BRM were localised within inducible bronchus-associated lymphoid tissues (iBALT) and displayed phenotypic and transcriptional signatures reminiscent of tissue-resident T cells, distinct from classical memory B cells in the blood or secondary lymphoid sites.

2021-11-18 | GSE159383 | GEO

Heterogeneity of LN resident macrophage

Project description:LN resident macrophages lining the lymphatic sinuses play critical roles in antigen capture and presentation as well as degradation. We used microarray to examine global gene expression profiles to compare SCS and med macrophages to determine the underlying molecular basis of their differential handling of antigens. Primary SCS and med macrophages were isolated and purified from LNs by flourescence-activated cell sorting and RNA extracted, amplified and hybridized for Affymetrix analysis.

2009-06-05 | E-GEOD-15767 | biostudies-arrayexpress

Transcriptional and phenotypic profile of lung-resident memory B cells induced by influenza infection

Project description:Transcriptional and phenotypic profile of lung-resident memory B cells induced by influenza infection

| PRJNA668738 | ENA

Assessing chromatin accessibility in WT and STAT4-/- ILC1s

Project description:STAT4 dynamically interacts with the genomic landscape and functions in modulating chromatin accessibility to influence gene expression. We aimed to evaluate the impact of STAT4 on chromatin accessibility of colonic lamina propria ILC1s. To address this aim, we sorted ILC1s from the colonic LP of unmanipulated C57BL/6 and STAT4-/- mice and performed the assay for transposase-accessible chromatin using sequencing (ATAC-seq).

2019-06-17 | GSE132769 | GEO

STAT4 ChIP-on-chip in IL12-Mediated T Helper 1 Cell Differentiation

Project description:The Signal Transducer and Activator of Transcription factor STAT4 is a critical component in the development of inflammatory adaptive immune responses. It has been extensively characterized as a lineage-determining factor in Th1 development. However, the genetic program activated by STAT4 that results in an inflammatory cell type is not well defined. In this report we use DNA isolated from STAT4-chromatin immunoprecipitation to perform ChIP-on-chip analysis of over 28,000 mouse gene promoters to identify STAT4 targets. We demonstrate that STAT4 binds multiple gene-sets that program distinct components of the Th1 lineage. While many STAT4 target genes display STAT4-dependent IL-12-inducible expression, other genes displayed IL-12-induced histone modifications but lack induction, possibly due to high relative basal expression. In the subset of genes that STAT4 programs for expression in Th1 cells, IL-12-induced mRNA levels remain increased for a longer time than mRNA from genes that are not programmed. This suggests that STAT4 binding to target genes, while critical, is not the only determinant for STAT4-dependent gene programming during Th1 differentiation. The supplementary bed file contains all 7504 Stat4 binding sites reported in the supplementary Analysis_results.xls Excel file.

2009-06-26 | GSE16845 | GEO

Genome-wide profiling of target genes for the systemic lupus erythematosus-associated transcription factors IRF5 and STAT4

Project description:IRF5 and STAT4 are strongly associated with human systemic lupus erythematosus (SLE). By performing chromatin immunoprecipitation-sequencing (ChIP-Seq) in human peripheral blood mononuclear cells (PBMCs), we identified more than 7000 target genes for IRF5 and STAT4 in stimulated PBMCs. Contrarily, without stimulation IRF5 seemed to be inactive, and STAT4 only showed low levels of transcriptional regulatory activity. Target genes of IRF5 and STAT4 were identified in human PBMCs with or without stimulation using ChIP-Seq.

2012-06-08 | E-GEOD-38567 | biostudies-arrayexpress

Regulating type 1 IFN effects in CD8 T cells during viral infections: changing STAT4 and STAT1 expression for function

Project description:Type 1 IFNs can conditionally activate all of the signal transducers and activators of transcription molecules (STATs), including STAT4. The best-characterized signaling pathways use STAT1, however, and type 1 IFN inhibition of cell proliferation is STAT1 dependent. We report that type 1 IFNs can basally stimulate STAT1- and STAT4- dependent effects in CD8 T cells, but that CD8 T cells responding to infections of mice with lymphocytic choriomenigitis virus have elevated STAT4 and lower STAT1 expression with significant consequences for modifying the effects of type 1 IFN exposure. The phenotype was associated with preferential type 1 IFN activation of STAT4 as compared to STAT1. Stimulation through the TCR induced elevated STAT4 expression, and STAT4 was required for peak expansion of antigen-specific CD8 T cells, low STAT1 levels, and resistance to type 1 IFN-mediated inhibition of proliferation. Thus, a mechanism is discovered for regulating the consequences of type 1 IFN exposure in CD8 T cells, with STAT4 acting as a key molecule in driving optimal antigen-specific responses and overcoming STAT1-dependent inhibition of proliferation. CD8 T cells were purified from uninfected WT, STAT1-deficient and STAT4-deficient mice or from D8 LCMV-infected WT mice and either control treated or treated with 1x104 U mouse IFNalpha for 90 minutes.

2012-09-07 | E-GEOD-40666 | biostudies-arrayexpress

CCR8 expression defines tissue-resident memory T cells in human skin

Project description:Human skin harbors two major T cell compartments of equal size that are distinguished by expression of the chemokine receptor CCR8. In vitro studies have demonstrated that CCR8 expression is under strict control of T cell antigen receptor (TCR)-engagement and the skin tissue microenvironment. We here examined the relationship between CCR8+ and CCR8− T cells. Phenotypic, functional, and transcriptomic analyses revealed that CCR8+ skin T cells bear all the hallmarks of resident memory T (TRM) cells, including homeostatic proliferation in response to IL-7 and IL-15, surface expression of tissue-localization (CD103) and -retention (CD69) markers, low levels of inhibitory receptors (PD-1, Tim-3, LAG-3), and a lack of senescence markers (CD57, KLRG1). In contrast, CCR8− skin T cells are heterogeneous and comprise variable numbers of exhausted (PD-1+), senescent (CD57+, KLRG1+), and effector (T-bethi, Eomeshi) T cells. Importantly, conventional and high-throughput analyses of expressed T cell receptor beta-chain (TRB) gene rearrangement sequences showed that the two skin memory T cell compartments distinguished by CCR8 expression are clonotypically distinct, suggesting that they are produced in response to separate antigenic challenges and distinct stimulatory conditions. Moreover, the phenotypic profiles of these populations were stable in vitro and the presence of similar levels of telomere erosion excludes the possibility of a linear differentiation pathway. In conclusion, CCR8 marks skin-specific, long-lived memory T cells. Therefore, we propose that CCR8+ T cells should be targeted in future skin vaccination research.

2017-12-11 | E-MTAB-6370 | biostudies-arrayexpress

Title: An IL-23-STAT4 Axis Regulates Classical Dendritic Cell Expansion and Function in Experimental Autoimmune Encephalomyelitis

Project description:The signal transducer and activator of transcription 4 (STAT4) promotes protective immunity and autoimmunity downstream of pro-inflammatory cytokines including IL-12 and IL-23. In experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), Stat4-/- mice are resistant to the development of inflammation and paralysis. Here, we examined cell-type requirements and found that in addition to T cells, STAT4 is required in dendritic cells for development of EAE. Deficiency of STAT4 in CD11c-expressing cells resulted in decreased T cell priming and inflammation in the CNS. EAE susceptibility was recovered following adoptive transfer of wild type bone marrow-derived DC to mice with STAT4-deficient DCs, but not adoptive transfer of STAT4- or IL-23R-deficient DCs. Single cell RNA-seq identified STAT4-dependent genes in DC subsets that paralleled a signature in MS patient DCs. Together, these data define a novel IL-23/DC/STAT4 pathway in DCs that could be a key to novel therapeutic targets in MS.

2024-07-17 | GSE243202 | GEO

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