Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA385951 | ENA |
REPOSITORIES: ENA
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Project description:Regulatory T cells (Treg) are a cornerstone of immune regulation. Recent evidence indicates that human Treg show plasticity in specific settings. A subpopulation of Treg expressing CD161, a marker associated with T helper (Th)17 cells, have T effector -like characteristics and are enriched at sites of autoimmune inflammation. Here we used RNAseq to confirm the effector-like signature of CD161+ Treg and demonstrated a shared transcriptional signature between CD161+ Treg and CD161+ conventional T cells (Tconv). Pathway analysis suggested that CD161+ T cells have a migratory phenotype, expressing high levels of CCR9 and integrin α4β7, markers associated with gut homing. In response to all-trans retinoic acid, CD161+ T cells expressed higher levels of CCR9 and integrin α4β7 than CD161- T cells. Our data suggest that blood CD161+ T cells may have adopted gut homing properties upon retinoic acid exposure. In contrast to their peripheral counterparts, CD161+ T cells from the site of autoimmune arthritis have a diminished gut homing phenotype and blunted response to retinoic acid. In health, the TCRβ repertoires of CD161+ and CD161- T cells showed limited overlap whereas there is clear overlap in T cell clones from synovial fluid of autoimmune arthritis patients. We therefore propose that CD161+ and CD161- T cells are largely distinct populations in the healthy immune system but that the inflamed site creates an environment where CD161 levels in T cells can be altered, potentially contributing to disease pathogenesis.
2017-03-27 | GSE86452 | GEO
Project description:CD69+CD103+ tissue-resident memory T-cells (TRM) are increasingly recognised as important drivers of inflammation. To decipher their potential role in inflammatory arthritis, we applied single cell, high-dimensional profiling (CyTOF and scRNAseq) to T-cells isolated from the joint of patients with psoriatic arthritis (PsA) or rheumatoid arthritis (RA). We identified three broad groups of synovial CD8+ TRM cells: cytotoxic and Treg-like TRM cells were present in the inflamed joints of patients with both PsA and RA, while CD161+CXCR6+ type 17-like TRM cells with a pro-inflammatory cytokine profile (IL-17A+TNFa+IFNg+) and a distinct transcriptomic signature and a polyclonal, but distinct TCR repertoire, were specifically enriched in the inflamed joints of patients with PsA. Type 17-like cells were also enriched in non-TRM CD8+ T-cells in PsA compared to RA. These findings add substantively to the accumulating evidence that the immunopathology of PsA and RA is different, with a particular role for type 17 cells in PsA.
2023-05-17 | GSE216914 | GEO
Project description:Innate immune cells, including dendritic cells (DCs), monocytes (Mono), macrophages (Mac), natural killer (NK) and innate lymphoid cells (ILC), contribute to chronic inflammation in lymphoid tissues. Here, we characterized the innate immune cell landscape in inflamed mesenteric lymph nodes (MLNs) of patients with inflammatory bowel diseases (IBD) at the single-cell level. CITE-seq analysis unveiled the molecular signature of 11 Mono/Mac/DC (MMDC) and 7 NK/ILC enriched clusters in human MLNs. DC clusters included 3 newly characterized DC clusters: CD1c/CD163/VCAN/CD64-expressing DC3; AXL-expressing DCs; and a CD103+ DC subset, expressing LTB, S100B, and IL22RA2 (encoding IL22BP). Mono/Mac clusters comprised inflammatory monocytes, which accumulated in IBD compared to non-IBD MLNs. Among NK/ILC clusters, we identified a cytotoxic ILC subset (IL7R, KLRD1, GNLY), previously not reported in MLNs, reminiscent of cytotoxic ILC1-like cells found in inflamed gut mucosa.
2025-05-26 | GSE284775 | GEO
Project description:CD161 is a C-type lectin like receptor expressed on the majority of Natural Killer (NK) cells, however, the significance of CD161 expression on NK cells has not been comprehensively investigated. We used microarrays to compare gene expression between healthy human CD161+ and CD161- NK cells.
2017-05-10 | GSE98702 | GEO
Project description:Inflammatory bowel diseases are associated with dysregulated immune responses in the intestinal tissue. Four molecularly identified macrophage subsets control immune homeostasis in healthy gut. However, the specific roles and transcriptomic profiles of the phenotypically heterogeneous CD14+ macrophage-like population in inflamed gut remain to be investigated in Crohn’s disease (CD). Here we identified two phenotypically, morphologically and functionally distinct colonic HLADR+SIRPα+CD14+ subpopulations that were further characterized using single-cell RNA-sequencing (scRNAseq) in CD. Frequencies of CD64hiCD163−/dim cells selectively augmented in inflamed colon and correlated with endoscopic score of disease severity. IL-1β and IL-23-producing CD64hiCD163−/dim cells predominated over TNF-α-producing CD64hiCD163hi cells in lesions. Purified “inflammatory monocyte-like” CD163−, but not “macrophage-like” CD163hi cells, through IL-1β, promoted Th17/Th1 but not Th1 responses in tissue memory CD4+T cells. Unsupervised scRNAseq analysis that captures the entire HLADR+SIRPα+ population revealed six clusters, two of which were enriched in either CD163− or CD163hi cells, and best defined by TREM1/FCAR/FCN1/IL1RN or CD209/MERTK/MRCI/CD163L1 genes, respectively. Selected newly identified discriminating markers were used beyond CD163 to isolate cells that shared pro-Th17/Th1 function with CD163− cells. In conclusion, a molecularly distinct pro-inflammatory CD14+ subpopulation accumulates in inflamed colon, drives intestinal inflammatory T-cell responses, and thus, might contribute to CD disease severity.
2019-11-09 | GSE140123 | GEO
Project description:Plasmacytoid dendritic cells (pDCs) are scarcely present in the inflamed human atherosclerotic plaque, where they are presumed to exert pro-inflammatory functions through release of type I interferons. However, the precise role of pDCs in human atherosclerosis yet remains to be established. We used microarrays to detail the global programme of gene expression underlying cellularisation and identified distinct classes of up-regulated genes during this process. We investigated the impact of human plaque pDCs on its local context, applying state of the art transcriptomics analysis on Laser Capture Microdissected fractions of human atherosclerotic plaques, distinctively enriched in pDCs, or pDCs-void.
2013-08-26 | E-GEOD-49670 | biostudies-arrayexpress
Project description:Plasmacytoid dendritic cells (pDCs) are scarcely present in the inflamed human atherosclerotic plaque, where they are presumed to exert pro-inflammatory functions through release of type I interferons. However, the precise role of pDCs in human atherosclerosis yet remains to be established. We used microarrays to detail the global programme of gene expression underlying cellularisation and identified distinct classes of up-regulated genes during this process.
2013-08-26 | GSE49670 | GEO
Project description:<p>Natural killer (NK) cells are forced to cope with different oxygen environments even under resting conditions. The adaptation to low oxygen is regulated by oxygen-sensitive transcription factors, the hypoxia-inducible factors (HIFs). The function of HIFs for NK cell activation and metabolic rewiring remains controversial. Activated NK cells are predominantly glycolytic, but the metabolic programs that ensure the maintenance of resting NK cells are enigmatic. By combining <em>in situ</em> metabolomic and transcriptomic analyses in resting murine NK cells, our study defines HIF-1a as a regulator of tryptophan metabolism and cellular nicotinamide adenine dinucleotide (NAD+) levels. The HIF-1a/NAD+ axis prevents ROS production during oxidative phosphorylation (OxPhos) and thereby blocks DNA damage and NK cell apoptosis under steadystate conditions. In contrast, in activated NK cells under hypoxia, HIF-1a is required for glycolysis, and forced HIF-1a expression boosts glycolysis and NK cell performance <em>in vitro</em> and <em>in vivo</em>. Our data highlight two distinct pathways by which HIF-1a interferes with NK cell metabolism. While HIF-1a-driven glycolysis is essential for NK cell activation, resting NK cell homeostasis relies on HIF-1a-dependent tryptophan/NAD+ metabolism.</p><p><br></p><p><strong>Linked cross omic data sets:</strong></p><p>RNA-seq data associated with this study are available in ArrayExpress (BioStudies): accession <a href='https://www.ebi.ac.uk/biostudies/arrayexpress/studies/E-MTAB-12082' rel='noopener noreferrer' target='_blank'>E-MTAB-12082</a>.</p>
2023-06-01 | MTBLS6863 | MetaboLights
Project description:The origin and function of human double negative (DN) TCR-alpha/beta T cells is unknown. They are thought to contribute to the pathogenesis of systemic lupus erythematosus because they expand and accumulate in inflamed organs. Here we provide evidence that human TCR-alpha/beta CD4- CD8- DN T cells derive exclusively from activated CD8+ T cells. Freshly isolated TCR-alpha/beta DN T cells display a distinct gene expression and cytokine production profile. DN cells isolated from peripheral blood as well as DN cells derived in vitro from CD8+ T cells, produce a defined array of pro-inflammatory mediators that includes IL-1, IL-17, IFN-gama, CXCL3, and CXCL2. These results indicate that, upon activation, CD8+ T cells have the capacity to acquire a distinct phenotype that grants them inflammatory capacity. TCR-alpha-beta+ CD25- T cells from healthy human individuals were sorted into CD4+, CD8+, and CD4-CD8- T cells. Cell lysis and RNA extraction was performed immediately. RNA from each cell subset was pooled.
2009-05-16 | E-GEOD-16130 | biostudies-arrayexpress
Project description:Understanding Natural Killer (NK) cell anatomical distribution is key to dissect the role of these unconventional lymphocytes in physiological and disease conditions. In mouse, NK cells have been detected in various lymphoid and non-lymphoid organs, while in humans the current knowledge of NK cell distribution at steady state is mainly restricted to lymphoid tissues. The translation to humans of findings obtained in mice is facilitated by the identification of NK cell markers conserved between these two species. The Natural Cytotoxicity Receptor (NCR) NKp46 is a marker of the NK cell lineage evolutionary conserved in mammals. In mice, NKp46 is also present on rare T cell subsets and on a subset of gut Innate Lymphoid Cells (ILCs) expressing the retinoic acid receptor-related orphan receptor gammat (RORgammat) transcription factor. Here, we documented the distribution and the phenotype of human NKp46+ cells in lymphoid and non-lymphoid tissues isolated from healthy donors. Human NKp46+ cells were found in splenic red pulp, in lymph nodes, in lungs and gut lamina propria, thus mirroring mouse NKp46+ cell distribution. We identified a novel cell subset of CD56dimNKp46low cells that includes RORgammat+ILCs with a lineage-CD94-CD117brightCD127bright phenotype.We also included data regarding the genome-wide transcriptional profiles of human healthy colonic NK cells and RORgammat+ILCs.The use of NKp46 thus contributes to establish the basis for analyzing quantitative and qualitative changes of NK cell and ILC subsets in human diseases. Human colonic CD56-NKp46lowCD117brightCD127bright cells = LTi cells and CD56+NKp46+CD117-CD127- cells =NK cells were isolated from macroscopically unaffected areas of colon of patients with colon cancer. Indicated populations were sorted and immediately lysed in RLT buffer supplemented with 10% beta-mercaptoethanol (Quiagen, France). Lysates of three distinct donors were pooled and RNA was isolated by using RNAeasy Microkit (Quiagen, France). Duplicates were performed for each cell type. cRNA were obtained after double amplification using the MessageAmp II aRNA Amplification Kit (Ambion, France). cRNA were then hybridized on Human Genome HG_U133 +2.0 Affymetrix chips. Chip images were generated using Affymetrix AGCC 3.2 software, then expression data were extracted and normalized using Affymetrix Expression console 1.1 with the algorithm RMA. Data obtained were expressed as log2.
2012-11-12 | E-GEOD-41469 | biostudies-arrayexpress