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GSE6566
Homo sapiens
4 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The strength of T cell stimulation determines IL-7 responsiveness, recall potential and lineage commitment of primed human CD4+IL-7Rhi T cells
Publication Title
The strength of T cell stimulation determines IL-7 responsiveness, secondary expansion, and lineage commitment of primed human CD4+IL-7Rhi T cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
Illumina HiSeq 2000
Description
Inflammation is a beneficial host response to infection, but it also contributes to inflammatory disease if unregulated. The Th17 lineage of T helper (Th) cells can cause severe human inflammatory diseases. These cells exhibit both instability (i.e., they can cease to express their signature cytokine, IL-17A) and plasticity (i.e., they can start expressing cytokines typical of other lineages) upon in vitro re-stimulation. However technical limitations prevented the transcriptional profiling of pre- and post-conversion Th17 cells ex vivo during immune responses. Thus, it is unknown whether Th17 cell plasticity merely reflects change in expression of a few cytokines, or if Th17 cells physiologically undergo global genetic reprogramming driving their conversion from one T helper cell type to another, a process known as “transdifferentiation”. Furthermore, while Th17 cell instability/plasticity has been associated with pathogenicity, it is unknown whether this could present a therapeutic opportunity, whereby formerly pathogenic Th17 cells could adopt an anti-inflammatory fate. Here we used two novel fate-mapping mouse models to track Th17 cells during immune responses to show that CD4+ T cells that formerly expressed IL-17A go on to acquire an anti-inflammatory phenotype. The transdifferentiation of Th17 into regulatory T cells was illustrated by a global change in their transcriptome and the acquisition of potent regulatory capacity. Comparisons of the transcriptional profiles of pre- and post-conversion Th17 cells also revealed a role for canonical TGF- ß signaling and the aryl hydrocarbon receptor (AhR) in conversion. Thus, Th17 transdifferentiate into regulatory cells, and contribute to the resolution of inflammation. Our data suggest Th17 cell instability and plasticity is a therapeutic opportunity for inflammatory diseases. Overall design: We isolated intestinal lymphocytes from two independent experiments, each using 5 mice injected with anti-CD3 mAb. Th17, exTh17, Tr1 exTh17, Tr1, Foxp3 Treg and Foxp3 IL-10+ Treg cell populations were FACS-sorted from these two independent experiments and the cells of each population were pooled before the analysis. Around 5,000 cells for each population were processed.
Publication Title
Th17 cells transdifferentiate into regulatory T cells during resolution of inflammation.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 2500
Description
IL-10 is a prototypical anti-inflammatory cytokine, which is fundamental to the maintenance of immune homeostasis, especially in the intestine. There is an assumption that cells producing IL-10 have an immunoregulatory function. However, here we report that IL-10-producing CD4+ T cells are phenotypically and functionally heterogeneous. By combining single cell transcriptome and functional analyses, we identified a subpopulation of IL-10-producing Foxp3Neg CD4+ T cells that displays regulatory activity unlike other IL-10-producing CD4+ T cells, which are unexpectedly pro-inflammatory. The combinatorial expression of co-inhibitory receptors is sufficient to discriminate IL-10-producing CD4+ T cells with regulatory function from others and to identify them across different tissues and disease models in mice and humans. These regulatory IL-10-producing Foxp3Neg CD4+ T cells have a unique transcriptional program, which goes beyond the regulation of IL-10 expression. Finally, we found that patients with Inflammatory Bowel Disease (IBD), demonstrate a deficiency in this specific regulatory T-cell subpopulation. Overall design: We carried out high troughput RNA sequencing of RNA isolated from IL-10 producing Foxp3- CD4+ T-cells, which were isolated from the spleen of mice treated with anti-CD3 antibody.
Publication Title
Molecular and functional heterogeneity of IL-10-producing CD4<sup>+</sup> T cells.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 36 Downloadable Samples
- Illumina HiSeq 2500
Description
By conditionally deleting BRD4 at various stages of thymic differentiation, we have established that BRD4 deficiency selectively affects a unique developmental subpopulation of thymocytes. Overall design: We examined by RNA-seq the effect on gene expression of BRD4 deletion in ex vivo DN, ISP, DP, CD4 and CD8 thymocyte subpopulations. The analysis was also performed on WT or BRD4 deleted ISP and DP thymocytes cultured for 16 hours at 37oC In this analysis, the conditional deletion of BRD4 (cKO) is achieved using the LCK-cre Transgene.
Publication Title
Immature CD8 Single-Positive Thymocytes Are a Molecularly Distinct Subpopulation, Selectively Dependent on BRD4 for Their Differentiation.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Macaca mulatta
- 6 Downloadable Samples
- Affymetrix Rhesus Macaque Genome Array (rhesus)
Description
Rhesus macaques (RMs) inoculated with live-attenuated Rev-Independent Nef simian immunodeficiency virus (Rev-Ind NefSIV) as adults or neonates controlled viremia to undetectable levels and showed no signs of immunodeficiency over 6-8 years of follow-up. We tested the capacity of this live-attenuated virus to protect RMs against pathogenic, heterologous SIVsmE660 challenges
Publication Title
Live attenuated Rev-independent Nef¯SIV enhances acquisition of heterologous SIVsmE660 in acutely vaccinated rhesus macaques.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 2000
Description
Method: mRNA profiles were generated from pair-end sequencing of duplicate samples using Illumina Hiseq 2000. Results: Genes with an expression change of more than 2 fold were considered to be differentially expresed Overall design: Macrophages are cells belongs to innate immune system, which response to pathogen by the production of inflammatory proteins those that are effective in both combating pathogen and wound healing. Using microarray approach with BET inhibitors it was shown that many of the inflammatory response genes were under control of BET proteins. Purpose of this study was to assess the effect of BRD4 KO in NGS derived transcriptome profiles of both stimulated and unstimulated macrophages.
Publication Title
BRD4 directs hematopoietic stem cell development and modulates macrophage inflammatory responses.
Sample Metadata Fields
Treatment, Subject
View Samples- Mus musculus
- 5 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Insulin-dependent diabetes is a complex multifactorial disorder characterized by
Publication Title
Identification of proliferative and mature β-cells in the islets of Langerhans.
Sample Metadata Fields
Sex, Specimen part
View Samples