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GSE14308
Mus musculus
12 Downloadable Samples
Description
Multipotential nave CD4+ T cells differentiate into distinct lineages including T helper 1 (Th1), Th2, Th17, and inducible T regulatory (iTreg) cells. The remarkable diversity of CD4+ T cells begs the question whether the observed changes reflect terminal differentiation with heritable epigenetic modifications or plasticity in T cell responses. We generated genome-wide histone H3 lysine 4 (H3K4) and lysine 27 (H3K27) trimethylation maps in nave, Th1, Th2, Th17, iTreg, and natural (n)Treg cells. We found that although modifications of signature cytokine genes (Ifng, Il4, and Il17) partially conform to the expectation of lineage commitment, critical transcription factors such as Tbx21 exhibit a broad spectrum of epigenetic states, consistent with our demonstration of T-bet and IFN-gamma induction in nTreg cells. Our data suggest an epigenetic mechanism underlying the specificity and plasticity of effector and regulatory T cells and also provide a framework for understanding complexity of CD4+ T helper cell differentiation.
Publication Title
No associated publication
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View Samples- Mus musculus
- 10 Downloadable Samples
Description
CD4+ T cells that selectively produce interleukin (IL)-17, are critical for host defense and autoimmunity1-4. Crucial for T helper17 (Th17) cells in vivo5,6, IL-23 has been thought to be incapable of driving initial differentiation. Rather, IL-6 and transforming growth factor (TGF)-1 have been argued to be the factors responsible for initiating specification7-10. Herein, we show that Th17 differentiation occurs in the absence of TGF- signaling. Neither IL-6 nor IL-23 alone efficiently generated Th17 cells; however, these cytokines in combination with IL-1 effectively induced IL-17 production in nave precursors, independently of TGF-. Epigenetic modification of the Il17a/Il17f and Rorc promoters proceeded without TGF-1, allowing the generation of cells that co-expressed Rort and T-bet. T-bet+Rort+ Th17 cells are generated in vivo during experimental allergic encephalomyelitis (EAE), and adoptively transferred Th17 cells generated with IL-23 in the absence of TGF-1 were more pathogenic in this experimental disease. These data suggest a new model for Th17 differentiation. Consistent with genetic data linking the IL23R with autoimmunity, our findings re-emphasize the role of IL-23 and therefore have important implications for the development of new therapies.
Publication Title
Generation of pathogenic T(H)17 cells in the absence of TGF-β signalling.
Sample Metadata Fields
Treatment
View Samples- Mus musculus
- 4 Downloadable Samples
Description
Furin is a proprotein convertase induced in activated T cells, reported to processes the anti-inflammatory cytokine TGFb-1. Herein, we show that conditional deletion of furin in T cells allowed for normal T cell development but impaired the function of regulatory T cells and effector cells, which produced less TGFb-1. Furin-deficient Treg cells, were less protective in a T cell transfer colitis model and failed to induce Foxp3 in normal T cells. Furin-deficient effector cells were inherently overly active and were resistant to suppressive activity of wild-type Tregs. Thus, our results indicate that furin is indispensable in maintaining peripheral tolerance, which is due, at least in part, to its nonredundant, essential function in regulating TGFb-1 production. Targeting furin has emerged as a strategy in malignant and infectious disease. The current work suggests that inhibiting furin might activate immune responses, but may result in a breakdown in peripheral tolerance.
Publication Title
No associated publication
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
Description
The different stages of the optic fissure can be clearly visualized by making sagittal sections through the mouse eye during early development which represent the optic fissure at open (E10.5), closing (E11.5) and fused (E12.5) states. Laser capture microdissection (LCM) was employed to dissect tissue from the margins of the optic fissure consisting of the outer (presumptive RPE) and inner (presumptive neurosensory retina) layers of the retina.
Publication Title
Expression profiling during ocular development identifies 2 Nlz genes with a critical role in optic fissure closure.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 48 Downloadable Samples
Description
Interleukin-17 (IL-17) is essential in host defense against extracellular bacteria and fungi, especially at mucosal sites, but it also contributes significantly to inflammatory and autoimmune disease pathologies. Binding of IL-17 to its receptor leads to recruitment of the adaptor protein CIKS/Act1 via heterotypic association of their respective SEFIR domains and to activation of the transcription factor NF-kB; it is not known whether CIKS and/or NF-kB are required for all gene induction events. Here we report that CIKS is essential for all IL-17 induced immediate-early genes in primary mouse embryo fibroblasts, while NF-kB is profoundly involved. We also identify a novel sub-domain in the N-terminus of CIKS that is essential for IL-17-mediated NF-kB activation. This domain is both necessary and sufficient for the interaction between CIKS and TRAF6, an adaptor required for NF-kB activation. The ability of decoy peptides to block this interaction may provide a new therapeutic strategy for intervention in IL-17-driven autoimmune and inflammatory diseases.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 44 Downloadable Samples
Description
Radiation lung injury is characterized by early inflammation and late fibrosis. The causes underlying the chronic, progressive nature of radiation injury are poorly understood. Here, we report that the gene expression of irradiated lung tissue correlates with that observed in the lungs in aged animals. We demonstrate that NOX4 expression and superoxide elaboration is increased in irradiated lungs and pneumocytes in a dose dependent fashion.
Publication Title
Role of type II pneumocyte senescence in radiation-induced lung fibrosis.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment, Time
View Samples- Mus musculus
- 32 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
No associated publication
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 26 Downloadable Samples
Description
In this study, we explored the molecular basis of site-specific metastasis of breast cancer to the lungs in a clinically relevant model based on the JygMC(A) cell line. In this dataset, we include expression data from JygMC(A) primary mammary tumors, lung metastases, normal mammary glands and normal lung parenchyma.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 18 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Mutant huntingtin's effects on striatal gene expression in mice recapitulate changes observed in human Huntington's disease brain and do not differ with mutant huntingtin length or wild-type huntingtin dosage.
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No sample metadata fields
View Samples- Mus musculus
- 17 Downloadable Samples
Description
Somatic mutation in the X-linked phosphatidylinositol glycan class A (PIG-A) gene causes glycosylphosphatidylinositol (GPI) anchor deficiency in humans with Paroxysmal Nocturnal Hemoglobinuria (PNH). Clinically, patients with PNH have intravascular hemolysis, venous thrombosis and bone marrow failure. We produced a conditional Pig-a knock-out mouse model specifically inactivating the Pig-a gene in hematopoietic cells to study the role of PIG-A deficiency in PNH pathophysiology. We used Affymetrix Mouse Genome 430 2.0 chips to investigate the gene expression pattern in the mouse model of targeted Pig-a deletion.
Publication Title
No associated publication
Sample Metadata Fields
No sample metadata fields
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