Exploring the organ specific expression pattern of CD4+iNKT1 cells of C57BL/6 and BALB/c mice.
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE160144 | GEO | 2021/11/18
REPOSITORIES: GEO
Similar Datasets
Project description:Exploring the organ specific expression pattern of CD4+iNKT1 cells of C57BL/6 and BALB/c mice.
| PRJNA672096 | ENA
Project description:iNKT cells can be classified based on functional criteria into iNKT1, iNKT2 and iNKT17 cells, respectively. Here, a protocol was applied allowing sorting of living cells from thumus of BALB/c and C57BL/6 mice. The obtained gene expression profiles confirmed already existing information regarding the iNKT subtypes and will therefore provide useful hints for further investigations.
2016-10-05 | GSE69120 | GEO
Project description:Invariant natural killer T (iNKT) cells are a rare but heterogenous T-cell subset with potent cytotoxic and immunomodulatory properties. During thymic development, murine iNKT cells go through different maturation stages and differentiate into distinct sublineages, namely iNKT1, iNKT2, and iNKT17 cells. Recent reports indicate that iNKT2 cells display immature properties and also give rise to other subsets, whereas iNKT1 cells seem to be terminally differentiated. Whether human iNKT cells follow a similar differentiation model is still unknown. To define the maturation stages and to assess the sublineage commitment of human iNKT cells during thymic development, in the present study we performed single-cell RNA sequencing analysis on human iNKT cells isolated from thymocytes. We show that human iNKT cells displayed heterogeneity and our unsupervised analysis identified two clusters: a first cluster expressed an immature profile with high expression of genes that are important for iNKT cell development and proliferation, whereas a second cluster displayed a mature, terminally differentiated profile. Trajectory analysis suggested an ontological relationship between the two clusters. Evaluation of the expression of sublineage-defining gene sets revealed that the first cluster contained mainly cells with an iNKT2 signature, whereas the more differentiated one contained cells that resembled murine iNKT1 cells. Our data point to the existence of different maturation stages of human thymic iNKT cells and provide evidence for sublineage commitment of iNKT cells in the human thymus.
2022-09-30 | GSE210956 | GEO
Project description:Functional subsets of iNKT cells, NKT1, NKT2 and NKT17, have been reported to arise during the thymus to peripheral differentiation stages. The key transcription factors for NKT1, NKT2 and NKT17 development in the thymus have been identified as T-bet, Gata3 and Rorγt, respectively. In contrast, these iNKT cell subsets can also undergo further differentiation in the periphery. Eomesodermin (Eomes) is a T-box transcription factor with high homology to T-bet and is expressed by activated CD8+ T cells as well as in resting and activated NK cells. However, its role in invariant (i)NKT cells remains unknown. Here, we show the impact of Eomes on iNKT cells in the thymus and peripheral tissue using conditional knockout (Eomes-cKO) mice. Eomes regulates the differentiation of NKT1 cells in the thymus. In the peripheral tissue, Klrg1+ iNKT1 cells are generated in lung after vaccination with -GalCer-pulsed DCs (DC/Gal) as memory like iNKT cells. In the current study, we found that Eomes also regulates their differentiation into memory-like KLRG1+iNKT cells in the periphery.
2019-05-09 | GSE128069 | GEO
Project description:Invariant Natural Killer T (iNKT) cells are a T cell subset with potent immunomodulatory properties. Experimental evidence in mice and observational studies in humans indicate that iNKT cells have antitumor potential as well as the ability to suppress acute and chronic Graft-versus-Host-Disease (GvHD). Murine iNKT cells differentiate during thymic development into iNKT1, iNKT2 and iNKT17 sublineages, which differ transcriptomically and epigenomically, and have subset-specific developmental requirements. Whether distinct iNKT sublineages also differ in their antitumor effect and their ability to suppress GvHD is currently unknown. In this work, we generated highly purified murine iNKTsublineages, characterized their transcriptomic and epigenomic landscape, and assessed specific functions. We demonstrate that iNKT2 and iNKT17, but not iNKT1 cells, efficiently suppress T cell activation in vitro and mitigate murine acute GvHD in vivo. Conversely, we show that iNKT1 cells display the highest antitumor activity against murine B-cell lymphoma cells both in vitro and in vivo. Thus, we demonstrate for the first time that iNKT sublineages have distinct and different functions, with iNKT1 cells having the highest antitumor activity and iNKT2 and iNKT17 cells having immune-regulatory properties. These results have important implications for the translation of i
2021-04-23 | GSE172169 | GEO
Project description:Respiratory syncytial virus (RSV) a leading cause of pediatric and adult morbidity and mortality worldwide. It can cause complications in multiple organs, thus increasing hospital stays and costs. However, RSV-based studies have primarily focused on effects in the lungs and blood, thereby potentially neglecting critical genes and pathways. Hence, studying RSV infection via a novel multi-organ approach is important. In this study, lung, intestine, brain, and spleen tissues from six BALB/c mice (6–8 weeks old; three in control group and three in RSV-infected group) were subjected to RNA sequencing. Differentially expressed genes (DEGs) in each organ were obtained and functional enrichment analysis was performed. We first used CIBERSORT to evaluate the immune-infiltration landscape. Subsequently, common DEGs (co-DEGs) among the four organs were analyzed to identify key genes and pathways. After quantitative reverse transcription-polymerase chain reaction, western blotting, and external validation analysis of key hub genes, their correlation with immune cells and potential functions were explored. We found that the host response to RSV infection varied among the four organs regarding gene expression profiles and immune cell infiltration. Analysis of the 16 co-DEGs indicated enrichment in the platelet and neutrophil degranulation pathways. Importantly, the key gene hemopexin (Hpx) was strongly correlated with the immune cell fraction in the lungs and may participate in the regulation of platelet activation and immune response.
2022-04-24 | GSE197868 | GEO
Project description:Three major phenotypically and functionally distinct invariant Natural Killer T (iNKT) cell subsets (iNKT1, iNKT17 and iNKT2), each with propensity to traffic to different tissues and to secrete different cytokines upon activation, have been defined. These fate assignments can be conferred upon iNKT cells during development in the thymus, but the cues that direct these decisions remain unclear. Here, we show that T cell antigen receptor (TCR) signal strength governs the development of iNKT cell subsets in the thymus, with high signaling strength necessary for iNKT2 and iNKT17 development. Alteration of TCR diversity and/or signaling dramatically diminished iNKT2 and iNKT17 cell subset development in a cell intrinsic manner. Decreased TCR signaling affected the persistence of Egr2 expression and the upregulation of PLZF both in vivo and in vitro. Genome-wide chromatin accessibility analysis revealed subset-specific activity of regulatory elements associated with unique signatures of transcription factor binding sites. NFAT and Egr binding motifs were found preferentially enriched in chromatin regulatory regions specifically accessible in iNKT2 cells that were lost in iNKT2 cells that had developed with reduced TCR signaling. Altogether, these data suggest a model of iNKT cell subset development where variable TCR signaling induces changes in chromatin accessibility at NFAT and Egr binding sites which exerts a determinative influence on the dynamic of gene enhancer accessibility that affects the developmental fate of iNKT cells.
2018-05-17 | GSE110327 | GEO
Project description:Three major phenotypically and functionally distinct invariant Natural Killer T (iNKT) cell subsets (iNKT1, iNKT17 and iNKT2), each with propensity to traffic to different tissues and to secrete different cytokines upon activation, have been defined. These fate assignments can be conferred upon iNKT cells during development in the thymus, but the cues that direct these decisions remain unclear. Here, we show that T cell antigen receptor (TCR) signal strength governs the development of iNKT cell subsets in the thymus, with high signaling strength necessary for iNKT2 and iNKT17 development. Alteration of TCR diversity and/or signaling dramatically diminished iNKT2 and iNKT17 cell subset development in a cell intrinsic manner. Decreased TCR signaling affected the persistence of Egr2 expression and the upregulation of PLZF both in vivo and in vitro. Genome-wide chromatin accessibility analysis revealed subset-specific activity of regulatory elements associated with unique signatures of transcription factor binding sites. NFAT and Egr binding motifs were found preferentially enriched in chromatin regulatory regions specifically accessible in iNKT2 cells that were lost in iNKT2 cells that had developed with reduced TCR signaling. Altogether, these data suggest a model of iNKT cell subset development where variable TCR signaling induces changes in chromatin accessibility at NFAT and Egr binding sites which exerts a determinative influence on the dynamic of gene enhancer accessibility that affects the developmental fate of iNKT cells.
2018-05-18 | GSE111427 | GEO
Project description:we compare the TCR repertoires of MAIT1 and MAIT17 cells from the mouse thymus using 5’ scRNAseq and scTCRseq of MR1:5-OP-RU tetramer positive thymocytes. A thorough analysis of TCR features between MAIT sub-populations did not show any difference between the repertoires of MAIT1 and MAIT17 subsets. Quantitative simulation of clonotype distributions of MAIT1 and MAIT17 cells allowed us to investigate the role of TCR characteristics in MAIT fate choice, and to pinpoint the stage at which lineage commitment occurs. Our results indicate that the TCR characteristics are not instructive in MAIT lineage choice and that MAIT1/17 commitment takes place during MAIT cell proliferation in the thymus. Finally, we performed analogous analysis of a published scRNA-seq and scTCR-seq dataset of iNKT from mouse thymus and demonstrated that our conclusions are also relevant for iNKT1 vs iNKT17 fate commitment.
2024-04-10 | GSE236666 | GEO
Project description:The goal of this study was to compare the gene expression program of iNKT1 cells in the thymus, liver and spleen. To to identify iNKT1 cells we created Tbx21Cre bacterial artifical chromosome transgenic mice with a Rosa26-floxed-stop-YFP reporter. We examined gene expression by RNA-sequencing in sorted iNKT1 cells (CD1d-Tet-PBS57+ YFP+) from the thymus, liver and spleen. Reads were aligned to the mm10 reference genome using Tophat v 2.1.0. Reads were assigned to genes using the htseq-count tool from HTSeq v 0.6.1 and gene annotations from Ensembl release 78. Differential expression was calculated across 3 independent replicates by EdgeR. We found that iNKT1 cells from all tissues had very similar gene expression programs but that there were subtle difference in each tissue that may have relevance for survival and function in these tissues.
2022-10-15 | GSE215338 | GEO