Similar Datasets
Project description:Single-cell RNAseq profiling of mouse invariant NKT thymocytes
| PRJNA595123 | ENA
Project description:Natural killer T (NKT) cells are positively selected on cortical thymocytes expressing the non-classical major histocompatibility complex (MHC) class I CD1d molecules. However, it is less clear how NKT cells are negatively selected in the thymus. In this study, we investigated the role of MHC class II expression in NKT cell development. Transgenic mice expressing MHC class II on thymocytes and peripheral T cells had a marked reduction in invariant NKT (iNKT) cells. Reduced numbers of iNKT cells correlated with the absence of in vivo production of cytokines in response to the iNKT cell agonist alpha-galactosylceramide. Using mixed bone marrow chimeras, we found that MHC class II-expressing thymocytes suppressed the development of iNKT cells in trans in a CD4-dependent manner. Our observations have significant implications for human iNKT cell development as human thymocytes express MHC class II, which can lead to an inefficient selection of iNKT cells.
| S-EPMC2801351 | biostudies-literature
Project description:Invariant Natural killer T (iNKT) cells are a separate lineage of T lymphocytes with innate effector functions. They express an invariant TCR specific for lipids presented by CD1d and their development and effector differentiation rely on a unique gene expression program. We asked whether this program includes microRNAs, small non-coding RNAs that regulate gene expression posttranscriptionally and play key role in the control of cellular differentiation programs. We identified a miRNA profile specific for iNKT cells, which exhibits features of activated/effector T lymphocytes. In this experiment we compared microRNAs of NKT cells versus those of conventional T lymphocytes, both extracted from wild type mouse thymus. To produce the populations we enriched mature thymocytes and then sorted NKT cells and conventional T cells (from one sorting we obtain one â??NKTâ?? sample and one â??Tâ?? sample). We performed the experiment in triplicate; the sample NKT 1 was sorted the same day of the sample T 1, NKT 2 with T 2, NKT 3 with T 3. We used a common reference approach for the 6 samples; as a common reference we produced RNA from total thymocytes, without the enrichment for mature cells and without the sorting; we pooled thymocytes derived from all the thymi used in the study. The aim of the experiment was to demonstrate that NKT cells have a microRNA profile different from that of conventional T cells.
2010-04-09 | E-GEOD-15925 | biostudies-arrayexpress
Project description:Thymocytes were extracted from a pool of three 8-12 week old C57BL-6 female mice. Cells were separated from stroma by gently crushing the thymi in between 2 microslides. RNA from thymocytes was extracted using the Trizol reagent and protocol, and analysed using the Illumina HiSeq 2000.
2016-04-15 | GSE75598 | GEO
Project description:Aim of the experiment was to characterize the gene activation profile<br><br>induced within immature myeloid DCs by cell-cell contact with activated<br><br>invariant NKT cells under steady-state conditions.
2010-10-08 | E-MEXP-2938 | biostudies-arrayexpress
Project description:Various subsets of invariant natural killer T (iNKT) cells with different cytokine productions develop in the mouse thymus, but the factors driving their differentiation remain unclear. Here we show that hypomorphic alleles of Zap70 or chemical inhibition of Zap70 catalysis lead to an increase of IFN-g-producing iNKT cells (NKT1 cells), suggesting NKT1 cells may require a lower TCR signal threshold. Zap70 mutant mice develop IL-17-dependent arthritis. iNKT cells and therapeutic induction of IFN-g secretion by activating iNKT cells are protective in this model, but the representation of IFNg versus IL-17 secreting iNKT cells in the joint change in favor of IL-17 producers as disease worsened. NKT1 cells are also present in the synovial fluid of arthritis patients, where they could be beneficial. Our data therefore suggest that TCR signal strength during thymic differentiation may influence not only IFNg production, but also the protective function of iNKT cells in arthritis.
2018-05-18 | GSE114594 | GEO
Project description:Various subsets of invariant natural killer T (iNKT) cells with different cytokine productions develop in the mouse thymus, but the factors driving their differentiation remain unclear. Here we show that hypomorphic alleles of Zap70 or chemical inhibition of Zap70 catalysis lead to an increase of IFN-g-producing iNKT cells (NKT1 cells), suggesting NKT1 cells may require a lower TCR signal threshold. Zap70 mutant mice develop IL-17-dependent arthritis. iNKT cells and therapeutic induction of IFN-g secretion by activating iNKT cells are protective in this model, but the representation of IFNg versus IL-17 secreting iNKT cells in the joint change in favor of IL-17 producers as disease worsened. NKT1 cells are also present in the synovial fluid of arthritis patients, where they could be beneficial. Our data therefore suggest that TCR signal strength during thymic differentiation may influence not only IFNg production, but also the protective function of iNKT cells in arthritis.
2018-05-17 | GSE114555 | GEO
Project description:Semi-invariant natural killer T (NKT) cells are thymus-derived innate lymphocytes that modulate microbial and tumour immunity as well as autoimmune diseases. These immunoregulatory properties of NKT cells are acquired during their development. Much has been learnt regarding the molecular and cellular cues that promote NKT cell development, yet how these cells are maintained in the thymus and the periphery and how they acquire functional competence are incompletely understood. We found that IL-15 induced several Bcl-2 family survival factors in thymic and splenic NKT cells in vitro. Yet, IL15-mediated thymic and peripheral NKT cell survival critically depended on Bcl-xL expression. Additionally, IL-15 regulated thymic developmental stage 2 (ST2) to ST3 lineage progression and terminal NKT cell differentiation. Global gene expression analyses and validation revealed that IL-15 regulated Tbx21 (T-bet) expression in thymic ST3 NKT cells. The loss of IL15-dependent T-bet expression resulted in poor expression of IFN-γ and several NK cell receptors in NKT cells. Taken together, our findings reveal a critical role for IL-15 in NKT cell survival, which is mediated by Bcl-xL, and effector differentiation, which is regulated by T-bet. Gene expression was measured in NKT cells sorted from pooled thymi of wild-type (3 replicates) or IL-15 deficient (2 replicates) mice.
2011-12-08 | E-GEOD-32568 | biostudies-arrayexpress
Project description:Invariant Natural killer T (iNKT) cells are a separate lineage of T lymphocytes with innate effector functions. They express an invariant TCR specific for lipids presented by CD1d and their development and effector differentiation rely on a unique gene expression program. We asked whether this program includes microRNAs, small non-coding RNAs that regulate gene expression posttranscriptionally and play key role in the control of cellular differentiation programs. We identified a miRNA profile specific for iNKT cells, which exhibits features of activated/effector T lymphocytes.
2009-07-01 | GSE15925 | GEO
Project description:Wild type thymi were transplanted into wild recipients (turnover) or Rag2-/-gc-/- mice (autonomy) and, after 28 days of transplant, thymocytes (double negative 3 and 4, immature CD8 single positive and CD4 CD8 double positive) were sorted and single cell RNAseq and TCR repertoire analysis performed
2021-04-12 | GSE160135 | GEO