Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Single-cell RNA-seq analysis identifies the atlas of lymph fluid and reveal a sepsis-related T cell subset

ABSTRACT: The lymphoid cycle as the sentinel of immune response, its cell subtypes and immune properties and functions during sepsis are still unclear. This study described a comprehensive picture of immune cells in rat lymph fluid by single-cell RNA sequencing and identified a unique subset of CD4+ T cells (CD4_Icos) in the early state of sepsis, confirming its crucial role in Treg cell production. Transferring with CD4+Icos+ T cells significantly alleviated CLP-induced organ injury, while Icosfl/flCd4-CreERT2 mice showed reduced number of Treg and increased inflammation and mortality risk. Further screening and validation experiments identified Npas2 as an Icos-specific transcription factor that regulates Icos expression and promotes the differentiation of CD4+Icos+ T cells. Clinical results disclosed the negative correlation between the expression of ICOS in CD4+ T cells and SOFA score in septic patients, which affected the prognosis of septic patients. These findings indicated the protective role of CD4+ T cells in sepsis.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE285325 | GEO | 2026/06/06

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

JunB plays a crucial role in the development of regulatory T cells by regulating interleukin-2 signaling

Project description:The AP-1 transcription factor JunB is crucial for multiple biological processes, such as placental development and bone homeostasis. We recently reported that JunB plays an essential role in development of Th17 cells, and thus Junb-deficient mice are resistant to experimental autoimmune encephalomyelitis. However, the role of JunB in CD4+ T cells under other inflammatory disease conditions is unknown. Here we show that mice lacking JunB in CD4+ T cells (Junbfl/flCd4-Cre mice) were more susceptible to dextran sulfate sodium (DSS)-induced colitis, a disease model induced by innate immune cells. While the Th17-associated genes Il17a and Il22 are shown to be protective against DSS-induced colitis, their expression was not impaired in the colon of Junbfl/flCd4-Cre mice. In addition to the defect in Th17 development, the colon of Junbfl/flCd4-Cre mice exhibited reduction in regulatory T (Treg) cells. Junb-deficient CD4+ T cells needed high concentration of IL-2 for differentiating into Treg cells in vitro because of their hyporesponsiveness to IL-2. Mechanistically, JunB directly up-regulated expression of CD25, the α−chain of high affinity IL-2 receptor, thereby increasing a sensitivity to IL-2 under Treg-inducing conditions. We uncover a crucial role for JunB in development of Treg cells and defense against an epithelial cell damage-induced colitis.

2020-03-31 | GSE120814 | GEO

JunB plays a crucial role in the development of regulatory T cells by increasing a sensitivity to interleukin-2

2022-03-31 | GSE131292 | GEO

Gene expression profile of conventional T cells (Tconv) and regulatory T cells (Treg) stimulated with anti-costimulatory molecule antibodies

Project description:Co-stimulatory molecules of the CD28 family on T lymphocytes integrate cues from innate immune system sensors, and modulate activation responses in conventional CD4+ T cells (Tconv) and their FoxP3+ regulatory counterparts (Treg). To better understand how costimulatory and co-inhibitory signals might be integrated, we profiled the changes in gene expression elicited in the hours and days after engagement of Treg and Tconv by anti-CD3 and either anti-CD28, -CTLA4, -ICOS, -PD1, -BTLA or -CD80. Total CD4+ T cells were stimulated by anti-CD3 and either anti-CD28, -CTLA4, -ICOS, -PD1, -BTLA or -CD80 antibodies for 1, 4, 20 and 48 hrs and Tconv and Treg were separated by flowcytometry. The 1 and 4 hr lysates were pooled [the 'early' samples] before RNA purification and profiling, as were the 20 and 48 hr samples [the 'late' samples] (note; for Treg cells, only the 20 hr sample was used). RNA was amplified, labeled and hybridized to Mouse Gene 1.0 ST arrays with the data generation and quality control pipeline of 19 the Immunological Genome Project (www.immgen.org), in biological triplicates (duplicates only for ICOS and CD80). Raw data were background-corrected and normalized using the RMA algorithm.

2012-11-15 | E-GEOD-42276 | biostudies-arrayexpress

Transcription profiling of mouse splenic CD4+ cells after surgical induction of sepsis vs. controls reveals a distinct transcriptional response 6 hours after sepsis induction

Project description:Lymphocytes are adversely affected during sepsis. Some CD4+ splenocytes undergo apoptosis while others become Th2 polarized. The molecular determinants of these phenotypic changes are not known. Here we compare the transcriptional response of septic CD4 splenocytes to CD4 splenocytes from sham-manipulated animals 6h after sepsis and identify an early transcriptional component to the septic CD4+ splenocyte phenotype. CD4+ splenocytes were isolated 6h after the surgical induction of sepsis for RNA extraction and hybridization on Affymetrix microarrays. We sought to obtain a homogeneous cell population in order to reduce any effects of cellular heterogeneity on expression profiles. To that end, immunomagnetic negative selection was used to enrich CD4+ splenocyte populations to ~91%. (n=5 biological replicates each CLP and sham)

2007-12-07 | E-GEOD-4479 | biostudies-arrayexpress

Expression data from CD4+ splenocytes 6h post-sepsis

Project description:Lymphocytes are adversely affected during sepsis. Some CD4+ splenocytes undergo apoptosis while others become Th2 polarized. The molecular determinants of these phenotypic changes are not known. Here we compare the transcriptional response of septic CD4 splenocytes to CD4 splenocytes from sham-manipulated animals 6h after sepsis and identify an early transcriptional component to the septic CD4+ splenocyte phenotype. We used microarrays to detail the global program of gene expression underlying the sepsis-induced changes in CD4+ splenocyte phenotype. Keywords: disease state analysis

2006-06-01 | GSE4479 | GEO

Whole blood transcriptome analysis of Septic shock patients according to early therapy response

Project description:Septic shock is the most severe complication of sepsis, associated with high mortality. The patient’s response to supportive therapy is very heterogeneous and the underlying mechanisms are still elusive. In order to identify which are the actors (genes and pathways) that play a role in establishing the response, we investigate the whole blood transcriptome in septic shock patients with positive and negative responses to early supportive hemodynamic therapy, assessed by changes in SOFA scores within the first 48 hours from ICU admission. We pinpointed genes and pathways that are differently modulated and enriched respectively within 48hrs between responders and non-responders.

2018-12-03 | GSE110487 | GEO

Single cell RNA sequencing of paired non small cell lung carcinoma tissue and peripheral blood from 5 donors

Project description:The immunosuppressive tumour microenvironment constitutes a significant hurdle to immune checkpoint inhibitors response. Both soluble factors and specialised immune cells such as regulatory T cells (TReg) are key components of active intratumoural immunosuppression. Previous studies have shown that Inducible Co-Stimulatory receptor (ICOS) can be highly expressed in the tumour microenvironment, especially on immunosuppressive TReg, suggesting that it represents a relevant target for preferential depletion of these cells. Here, we performed immune profiling of samples from paired tumour and peripheral blood of 5 patients with non-small cell lung cancer (NSCLC). We found Icos mRNA expression in NSCLC samples was higher in TRegs than in other T cell subsets and higher in the TME than in the periphery with the expression pattern in both compartments following the general trend of: TReg > CD4non-TReg > CD8 > Other.

2020-09-01 | E-MTAB-9451 | biostudies-arrayexpress

PD-1+ and PD-1- CD4+ Teff and Treg cells in Glioblastoma and Health

Project description:<p>PD-1 is an important immune checkpoint inhibitor that shows great promise in the clinic, particularly for melanoma and lung cancers. Since PD-1 is also expressed on infiltrating CD4+ Treg and Teffector cells in glioblastoma, we sought to better understand the role of PD-1 on these infiltrating CD4+ Treg and Teffector cells. To this end, we performed functional and transcriptional profiling using CD4+ Treg and Teffector cells isolated from healthy donors and glioblastoma patients (from both tumors and blood).</p>

| phs001079 | dbGaP

scRNA-seq of human Tfh, Tfr and Treg cells sorted from Tonsil, Iliac Lymph Node and PBMCs

Project description:The datasets were obtained to investigate the transcriptional profile of Tfh, Tfr and Treg cells isolated from different human tissues. The comparison between lymphoid tissues with different frequency of the most mature Tfh and Tfr cells allows the investigation of maturation as well as tissue adaptation of those different cell subsets. To address these issues, three different cell populations from three different tissues were sorted by index sorting, with Tfh cells as CD4+CXCR5+ICOS+; Tfr cells as CD4+CXCR5+CD25+ and Treg cells as CD4+CXCR5-CD25+. Smart-seq2 protocol was used mRNA library preparations.

2021-04-22 | E-MTAB-10364 | biostudies-arrayexpress

Whole blood transcriptome of survivors and nonsurvivors of sepsis

Project description:There is currently no reliable tool available to measure immune dysfunction in septic patients in the clinical setting. This proof-of-concept study assesses the potential of gene expression profiling of whole blood as a tool to monitor immune dysfunction in critically ill septic patients. Whole blood samples were collected daily for up to 5 days from patients admitted to the intensive care unit with sepsis. RNA isolated from whole blood samples was assayed on Illumina HT-12 gene expression microarrays consisting of 48,804 probes. Microarray analysis identified 3677 genes as differentially expressed across 5 days between septic patients and healthy controls. Of the 3677 genes, biological pathway analysis identified 86 genes significantly down-regulated in the sepsis patients were present in pathways relating to immune response. These 86 genes correspond to known immune pathways implicated in sepsis including lymphocyte depletion, reduced T lymphocyte activation and deficient antigen presentation. Furthermore, expression levels of these genes correlated with clinical severity, with a significantly greater degree of down-regulation found in non-survivors compared to survivors. The results show that whole blood gene-expression analysis can capture systemic immune dysfunctions in septic patients. Our study provides an experimental basis to support further study on the use of a gene expression based assay, to assess immunosuppression and guide immunotherapy in future clinical trials. Daily PAXgene samples for up to 5 days for sepsis survivors (n=26), sepsis nonsurvivors (n=9), and healthy controls (n=18).

2014-02-04 | E-GEOD-54514 | biostudies-arrayexpress