Positive selection occurs in the thymic cortex, but critical maturation events occur later in the medulla. We defined the precise stage at which T cells acquire competence to proliferate and emigrate. Transcriptome analysis of late gene changes suggested roles for NF-B and interferon signaling. Mice lacking the IKK kinase TAK1, showed normal positive selection, but a specific block in functional maturation. NF-B signaling provided protection from TNF, and was required for proliferation and emigration. Alternatively, the interferon signature was independent of NF-B, and IFNR deficient thymocytes showed reduced STAT1 levels and phenotypic abnormality, but were competent to proliferate. Thus, both NF-B and tonic IFN signals are involved in the final maturation of thymocytes into nave T cells.
Late stages of T cell maturation in the thymus involve NF-κB and tonic type I interferon signaling.
Specimen part
View SamplesEpithelial cells provide an initial line of defense against damage and pathogens in barrier tissues such as the skin; however this balance is disrupted in obesity and metabolic disease. Skin gamma delta T cells recognize epithelial damage and release cytokines and growth factors that facilitate wound repair. To determine the impact of obesity and metabolic disease on skin gamma delta T cells, we isolated skin gamma delta T cells from 10-week old C57BLKS/J lean db/+ and obese db/db animals for further study. Due to a deficiency in the leptin receptor (db), homozygous db/db animals do not process satiety signals, continually eat and develop severe obesity and metabolic disease. Skin gamma delta T cells isolated from these animals were compared for changes in mRNA expression using microarray. We have determined that obesity and metabolic disease negatively impacts homeostasis and functionality of skin gamma delta T cells, rendering host defense mechanisms vulnerable to injury and infection.
Gammadelta T cells are reduced and rendered unresponsive by hyperglycemia and chronic TNFalpha in mouse models of obesity and metabolic disease.
No sample metadata fields
View SamplesMAPK scaffolds, such as IQGAP1, assemble pathway kinases together to effect signal transmission and disrupting scaffold function therefore offers a potentially orthogonal approach to MAPK cascade inhibition. Consistent with this possibility, we observed an IQGAP1 requirement in Ras-driven tumorigenesis in mouse and human tissue. Delivery of the IQGAP1 WW peptide sequence that mediates Erk1/4 binding, moreover, disrupted IQGAP1-Erk1/2 interactions, abolished Ras/Raf-driven tumorigenesis, bypassed acquired resistance to the B-Raf inhibitor vemurafinib (PLX- 4032), and acts as a systemically deliverable therapeutic to significantly increase lifespan of tumor bearing mice. Scaffold-kinase interaction blockade (SKIB) acts by a mechanism distinct from direct kinase inhibition and represents a strategy to target over-active oncogenic kinase cascades in cancer.
IQGAP1 scaffold-kinase interaction blockade selectively targets RAS-MAP kinase-driven tumors.
Time
View SamplesLymphocytes from spleen and lymph nodes of unimmunized adult C57BL/6 mice were isolated, stained with antibodies for flow cytometry, and sorted into the CD8+ CD44lo CD5hi and CD5lo pool
The TCR's sensitivity to self peptide-MHC dictates the ability of naive CD8(+) T cells to respond to foreign antigens.
Specimen part
View SamplesThe goal of this study is to determine the complete gene expression profile for each cell type of the developing gonad during the critical window in which it adopts the testis or ovarian fate.
Temporal transcriptional profiling of somatic and germ cells reveals biased lineage priming of sexual fate in the fetal mouse gonad.
Sex
View SamplesThe conserved multi-subunit Ccr4-Not complex regulates gene expression in diverse ways. In this work, we characterize the suppression of temperature sensitivity associated with a mutation in the gene encoding the scaffold subunit of the Ccr4-Not complex, NOT1, by the deletion of SPT3.
A SAGA-independent function of SPT3 mediates transcriptional deregulation in a mutant of the Ccr4-not complex in Saccharomyces cerevisiae.
No sample metadata fields
View SamplesWe tested the effects of co-infection on vaccine response to YFV-17D.
Sequential Infection with Common Pathogens Promotes Human-like Immune Gene Expression and Altered Vaccine Response.
Specimen part
View SamplesTranscriptional analysis of multiple brain regions in Parkinson's disease supports the involvement of specific protein processing, energy metabolism, and signaling pathways, and suggests novel disease mechanisms.
Transcriptional analysis of multiple brain regions in Parkinson's disease supports the involvement of specific protein processing, energy metabolism, and signaling pathways, and suggests novel disease mechanisms.
Sex, Age, Disease, Disease stage
View SamplesPost mortem tissue was dissected from two groups of age and gender matched groups of Parkinson and Control subjects
Transcriptional analysis of multiple brain regions in Parkinson's disease supports the involvement of specific protein processing, energy metabolism, and signaling pathways, and suggests novel disease mechanisms.
Sex, Age, Disease, Disease stage
View SamplesPost mortem tissue was dissected from two groups of age and gender matched groups of Parkinson and Control subjects
Transcriptional analysis of multiple brain regions in Parkinson's disease supports the involvement of specific protein processing, energy metabolism, and signaling pathways, and suggests novel disease mechanisms.
Sex, Age, Disease, Disease stage
View Samples