Foxp3+ regulatory T (Treg) cells prevent inflammatory disease but the mechanistic basis of suppression is not understood completely . Gene silencing by RNA interference can act in a cell-autonomous and non-cell-autonomous manner, providing mechanisms of inter-cellular regulation. Here, we demonstrate that non-cell-autonomous gene silencing, mediated by miRNA-containing exosomes, is a mechanism employed by Treg cells to suppress T cell-mediated disease. Treg cells transferred microRNAs (miRNA) to various immune cells, including T helper 1 (Th1) cells, suppressing Th1 cell proliferation and cytokine secretion. Use of Dicer-deficient or Rab27a and Rab27b double-deficient Treg cells to disrupt miRNA-biogenesis or the exosomal pathway, respectively, established a requirement for miRNAs and exosomes for Treg cell-mediated suppression. Transcriptional analysis and miRNA inhibitor studies showed that exosome-mediated transfer of Let-7d from Treg cell to Th1 cells contributed to suppression and prevention of systemic disease. These studies reveal a mechanism of Treg cell-mediated suppression mediated by miRNA-containing exosomes.
MicroRNA-containing T-regulatory-cell-derived exosomes suppress pathogenic T helper 1 cells.
Specimen part
View SamplesGene expression of Treg cells that have lost Foxp3 expression and acquired Il4 expression following adoptive transfer into T-cell deficient mice (HpTR-IL-4gfp+), cmpared to conventional Treg cells isolated from H. polygyrus-infected wild-type mice (HpTR) and Th2 cells generated from nave T cells following adoptive transfer into H. polygyrus-infected T-cell deficient mice (nT-IL-4gfp+).
Interleukin 4 promotes the development of ex-Foxp3 Th2 cells during immunity to intestinal helminths.
Specimen part
View SamplesImatinib has become the current standard therapy for patients with chronic myelogenous leukaemia (CML). For a better understanding of the Imatinib-related molecular effects in vivo, we assessed gene expression profiles of Philadelphia Chromosome positive (Ph+) CD34+ cells from peripheral blood of 6 patients with de novo CML in chronic phase. After 7 days of treatment with Imatinib the Ph+ CD34+ cells were reassessed to look for changes in the transcriptome. The expression level of 303 genes was significantly different comparing the transcriptome of the Ph+ CD34+ cells before and after 7 days of Imatinib therapy (183 down-regulated, 120 up-regulated, lower bound 1.2-fold). For a substantial number of genes governing cell cycle and DNA replication, the level of expression significantly decreased (CDC2, RRM2, PCNA, MCM4). On the other hand, therapy with Imatinib was associated with an increase of genes related to adhesive interactions, such as L-selectin or CD44. A group of 8 genes with differential expression levels were confirmed using a gene specific quantitative real-time PCR. Thus, during the first week of treatment, Imatinib is preferentially counteracting the bcr-abl induced effects related to a disturbed cell cycle and defective adhesion of leukemic Ph+ CD34+ cells.
Early in vivo changes of the transcriptome in Philadelphia chromosome-positive CD34+ cells from patients with chronic myelogenous leukaemia following imatinib therapy.
No sample metadata fields
View SamplesThis series includes the four major subtypes of pituitary adenomas and normal post-mortem pituitary tissue
Differential gene expression in pituitary adenomas by oligonucleotide array analysis.
No sample metadata fields
View SamplesProstate tumors contain foci of neuroendocrine transdifferentiation (NETD), resulting in an increase of androgen-independent neuroendocrine-like (NE) tumor cells, whose number significantly correlates with tumor aggressiveness and a lower survival rate. The mechanisms leading to NETD and the exact role of NE-like tumor cells in disease progression are not fully understood yet.
The deregulation of miR-17/CCND1 axis during neuroendocrine transdifferentiation of LNCaP prostate cancer cells.
Cell line, Treatment
View SamplesPrimary RNASeq data for progenitor, resident, and stimulated (C.alb, LPS, injury, APAP+ starved overnight and pIC) mononuclear phagocytes from fourteen organs. Overall design: RNASeq data for over 400 samples comprising of 130 populations submitted by 16 labs (both non-ImmGen and ImmGen labs) from 8 locations around the world for ImmGen OpenSource Mononuclear Project. Samples were sorted in these facilities using ImmGen's stringent ULI protocol and shipped to one location for library preparation and sequencing. Contributor: Immunological Genome Project Consortium
ImmGen report: sexual dimorphism in the immune system transcriptome.
Age, Specimen part, Cell line, Subject
View SamplesPrimary RNA Seq data for 11 diverse immunocyte populations from male and female mice of varying ages stimulated with different dose of IFN and sequenced using ImmGen's standard ultra-low input RNA-seq pipeline Overall design: RNASeq data for 11 cell populations from male and female mice generated by ImmGen labs to study sexual differences in the immune system (companion ATACseq datasets are found in GSE100738). These mice comprised of varying ages, including 6-8weeks and 2- 20months old. In addition, mice were stimulated with 1K and 10K Type 1 interferon to understand sex specific responses. contributor: Immunological Genome Project Consortium
ImmGen report: sexual dimorphism in the immune system transcriptome.
Sex, Age, Specimen part, Cell line, Subject
View SamplesWe expressed a constitutively active mutant of MEK5 (MEK5D) in human primary endothelial cells (EC) to study the transcriptional and functional responses to Erk5 activation under static conditions.
Erk5 activation elicits a vasoprotective endothelial phenotype via induction of Kruppel-like factor 4 (KLF4).
Cell line
View SamplesIt has long been known that leukemic cells disrupt normal patterns of blood cell formation, but little is understood about mechanisms. It has generally been assumed that normal hematopoietic stem and progenitor cells (HSPC) are simply out-competed for space by malignant cells. We designed a strategy to determine if leukemic cells alter intrinsic properties and functions of normal HSPCs. Chimeric mice were generated by transplantation of normal marrow and marrow from an inducible transgenic model of chronic myelogenous leukemia (CML). With induction of CML, the composition of the marrow changed dramatically, and normal HSPCs divided more readily and lost their ability to produce lymphocytes. In contrast, only modest changes were recorded in numbers of normal hematopoietic stem cells (HSCs). However, these stem cells were not unscathed, and had reduced reconstitution and self-renewal potential upon transplantation. Interestingly, the normal bystander cells acquired gene expression patterns resembling their neighboring malignant counterparts. This suggested that much of the leukemia signature is mediated by extrinsic factors in the environment.
Treatment of chronic myelogenous leukemia by blocking cytokine alterations found in normal stem and progenitor cells.
Specimen part
View SamplesThe intention of these gene expression analysis was to study host responses to an infection with Agrobacterium tumefaciens at different stages of crown gall development. Therefore the transcriptome of infected inflorescence stalk tissue and mature crown galls of Arabidopsis thaliana (WS-2) was determined of three different time points. These were compared with the transcriptome of mock-infected inflorescence stalk tissue (reference) of the same age. The following time points were analyzed: (i) three hours post inoculation, before the T-DNA is integrated into the host genome (ii) six days after inoculation when the T-DNA is present in the nucleus and the oncogenes are expressed in the host cell, and (iii) 35 days after inoculation when a mature tumors has developed. For the three-hour- (3hpi) and six-day- time point (6dpi) plants were infected with the virulent strain C58, harboring a T-DNA, or with strain GV3101, containing a disarmed Ti-plasmid. This allows discrimination between signals which derive from the bacterial pathogen and the T-DNA encoded oncogenes.
An integrated view of gene expression and solute profiles of Arabidopsis tumors: a genome-wide approach.
Specimen part
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