KLRG1 and NKp46 discriminate subpopulations of human CD117+ CRTH2- ILCs biased toward ILC2 or ILC3
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ABSTRACT:
PROVIDER: PRJNA509919 | ENA |
REPOSITORIES: ENA
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Project description:Recently, circulating multi- and uni-potential human ILC precursors (ILCP) have been found in a lymphocyte population that expresses CD117 and CD127 but lack CRTH2 and NKp44. However, these ILCPs have not been extensively characterized. We performed an unbiased Hierarchical Stochastic Neighbor Embedding (HSNE) analysis of the phenotype of peripheral blood CD117+ ILCPs which revealed the presence of three major subsets; the first expressed NKp46, the second expressed both NKp46 and CD56 and the third expressed KLRG1. Analysis of the differentiation potential of these cells on bulk and clonal levels, cytokine production and the transcriptome revealed that the NKp46+ ILCPs contain high frequencies of ILC3 precursors whereas a minority can differentiate into ILC1/NK-like cells. In contrast KLRG1+ ILCPs are biased to the ILC2 lineage, but are highly plastic and epigenetically poised to differentiate to other ILC subsets depending on the activation signals they receive.
2019-06-05 | GSE123817 | GEO
Project description:Recently, circulating multi- and uni-potent human ILC precursors (ILCP) have been found in a lymphocyte population that expresses CD117 and CD127 but lacks CRTH2 and NKp44. However, these ILCPs have not been extensively characterized. We performed an unbiased Hierarchical Stochastic Neighbor Embedding (HSNE) analysis of the phenotype of peripheral blood CD117+ ILCPs which revealed the presence of three major subsets: the first expressed NKp46, the second expressed both NKp46 and CD56, while the third expressed KLRG1. Analysis of their differentiation potential on bulk and clonal levels, cytokine production and the transcriptome revealed that the NKp46+ ILCPs contain high frequencies of ILC3 precursors whereas a minority can differentiate into ILC1/NK-like cells. In contrast, KLRG1+ ILCPs are biased to the ILC2 lineage, but are highly plastic and epigenetically primed to differentiate into other ILC subsets depending on the activation signals they receive.
2019-06-05 | GSE124054 | GEO
Project description:Recently, human ILCs that express CD117 and CD127 but lack CRTH2 and NKp44 have been shown to contain precursors of ILC1, ILC2, and ILC3. However, these ILCs have not been extensively characterized. We performed an unbiased hierarchical stochastic neighbor embedding (HSNE) analysis of the phenotype of peripheral blood CD117+ ILCs, which revealed the presence of three major subsets: the first expressed NKp46, the second expressed both NKp46 and CD56, and the third expressed KLRG1, but not NKp46 or CD56. Analysis of their cytokine production profiles and transcriptome revealed that NKp46+ ILCs predominantly develop into ILC3s; some of them can differentiate into ILC1/NK-like cells, but they are unable to develop into ILC2s. In contrast, KLRG1+ ILCs predominantly differentiate into ILC2s. Single-cell cultures demonstrate that KLRG1+ ILCs can also differentiate into other ILC subsets depending on the signals they receive. Epigenetic profiling of KLRG1+ ILCs is consistent with the broad differentiation potential of these cells.
| S-EPMC6683990 | biostudies-literature
Project description:The aim of this study was to analyze the global transcriptional profiles of small intestine (SI) Innate Lymphoid Cells (ILCs) expressing the NK cell marker NKp46. Based on differential expression of the RORgt transcription factor SI NKp46+ ILCs can be divided in NKp46+RORgt- and NKp46+RORgt+ cells. While NKp46+RORgt- cells produce IFN-g, like conventional Natural Killer (NK) cells, NKp46+RORgt+ cells secrete IL-22, like Lymphoid Tissue inducer (LTi) cells. We compared the global transcriptional profiles of both NKp46+RORgt- and NKp46+RORgt+ cells to conventional splenic NK cells and to SI NKp46-RORgt+ cells, which contain adult LTi cells. By following this approach, we showed that SI NKp46+RORγt- ILCs correspond to SI NK cells. We also identified a transcriptional program conserved in adult SI NKp46+RORγt+, NKp46-RORγt+ ILCs and fetal LTi. The various ILC cell populations analyzed in this study were isolated from C57BL/6 RORc(gt)+/GFP reporter mice. SI NKp46+RORγt- (NKp46+GFP-) cells, SI NKp46+RORγt+ cells (NKp46+GFPlow and NKp46+GFPhigh cells) and NKp46-RORγt+ ILCs, including adult LTi cells , were sorted by flow cytometry from CD3- lamina propria cells of small intestine (SI) of RORc(γt)+/GFP reporter mice . Splenic NKp46+RORγt- (NKp46+GFP-) cells were also sorted as the reference for conventional NK cells. Two replicates of each populations were produced and analyzed.
2011-06-20 | E-GEOD-29777 | biostudies-arrayexpress
Project description:KLRG1 and NKp46 expressing CD117+ human innate lymphoid cell precursors are biased to ILC2 and ILC3, respectively
| PRJNA510626 | ENA
Project description:The aim of this study was to analyze the global transcriptional profiles of small intestine (SI) Innate Lymphoid Cells (ILCs) expressing the NK cell marker NKp46. Based on differential expression of the RORgt transcription factor SI NKp46+ ILCs can be divided in NKp46+RORgt- and NKp46+RORgt+ cells. While NKp46+RORgt- cells produce IFN-g, like conventional Natural Killer (NK) cells, NKp46+RORgt+ cells secrete IL-22, like Lymphoid Tissue inducer (LTi) cells. We compared the global transcriptional profiles of both NKp46+RORgt- and NKp46+RORgt+ cells to conventional splenic NK cells and to SI NKp46-RORgt+ cells, which contain adult LTi cells. By following this approach, we showed that SI NKp46+RORγt- ILCs correspond to SI NK cells. We also identified a transcriptional program conserved in adult SI NKp46+RORγt+, NKp46-RORγt+ ILCs and fetal LTi.
2011-06-20 | GSE29777 | GEO
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
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.
2012-11-12 | GSE41469 | GEO
Project description:The goal of this study is to characterize the transcriptional profile of three memory CD8 T cell subsets: IL-7Rα+KLRG1- (memory precursors, MP), IL-7Rα+KLRG1+ (KLRG1+ MP) and IL-7Rα-KLRG1+ (terminal effectors, TE).
2022-12-12 | GSE218777 | GEO
Project description:Innate lymphoid cells (ILCs) are critically involved in intestinal adaptation to microenvironmental challenges (Colonna, 2018; Guendel et al., 2020) and the gut mucosa is characterized by low oxygen. Adaptation to low oxygen is mediated by Hypoxia-inducible transcription factors (HIFs) the HIF-1α subunit shapes the ILC phenotype upon acute experimental colitis and contributes to intestinal damage. However, the impact of HIF signaling in NKp46+ ILC in the context of repetitive mucosal damage and chronic inflammation, as it typically occurs during inflammatory bowel disease, is unknown. In a model of chronic colitis, mice lacking the HIF-1α isoform in NKp46+ ILCs show a decrease in NKp46+ ILC1s but a concomitant rise in neutrophils as well as Ly6C high macrophages. Single-nuclei RNA sequencing suggests enhanced interaction of mesenchymal cells with other cell compartments in the colon of HIF-1α KO mice and a loss of mucus-producing enterocytes as well as intestinal stem cells. This was, furthermore, associated with increased BMP-integrin signaling, expansion of profibrotic fibroblasts subsets and intestinal fibrosis. In summary this suggests that HIF-1 α mediated ILC1 activation, although detrimental upon acute colitis, protects against excessive inflammation and fibrosis during chronic intestinal damage.
2024-06-12 | GSE252602 | GEO