Recently, the bone marrow (BM) has been shown to play a key role in regulating the survival and function of memory T cells. However, the impact of aging on these processes has not yet been studied. We demonstrate that the number of CD4+ and CD8+ T cells in the BM is maintained during aging. However, the composition of the T cell pool in the aged BM is altered with a decline of nave and an increase in effector-memory T cells. In contrast to the peripheral blood (PB), a highly activated CD8+CD28 T cell population, which lacks the late differentiation marker CD57, accumulates in the BM of elderly persons. IL-6 and IL-15, which are both increased in the aged BM, efficiently induce the activation, proliferation and differentiation of CD8+ T cell in vitro, highlighting a role of these cytokines in the age-dependent accumulation of highly activated CD8+CD28 T cells in the BM. Yet, these age-related changes do not impair the maintenance of a high number of polyfunctional memory CD4+ and CD8+ T cells in the BM of elderly persons. In summary, aging leads to the accumulation of a highly activated CD8+CD28 T cell population in the BM, which is driven by the age-related increase of IL-6 and IL-15. Despite these changes, the aged BM is a rich source of polyfunctional memory T cells and may thus represent an important line of defense to fight recurrent infections in old age.
The impact of aging on memory T cell phenotype and function in the human bone marrow.
Sex, Age
View SamplesNeural crest cells migrate extensively in vertebrate embryos to populate diverse derivatives including ganglia of the peripheral nervous system.
Molecular Events Controlling Cessation of Trunk Neural Crest Migration and Onset of Differentiation.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Transcriptome and cytogenetic profiling analysis of matched in situ/invasive cutaneous squamous cell carcinomas from immunocompetent patients.
Sex, Age, Specimen part, Disease stage, Subject
View SamplesAlthough most cutaneous squamous cell carcinomas (cSCC) develop from actinic keratoses (AK), the key events for this evolution remain unclear. We have combined the results of different genomic and expression array platforms on matched samples of sun-exposed skin, AK and cSCC from ten immunocompetent patients, with the objective of better understanding the mechanisms involved in this progression. Gene expression analysis and copy number alterations were assessed using GeneChip Human Gene 2.0 ST Array (Affymetrix) and CytoScan HD Cytogenetics Solution (Affymetrix) platforms, respectively. Integration of genome and transcriptome results was evaluated using the DR-Integrator tool. Additional studies (qPCR, immunohistochemistry and Western blot) were performed for selected genes. Twenty-two genes showed a progressive expression spectrum from clinically normal sun-exposed skin samples to cSCC. FOSL1 and BNC1 encode transcription factors whose expression was increased in cSCC in the expression array and the qPCR. By immunohistochemistry, FOSL1 showed an intense staining at the invasive front of cSCC samples and BNC1 expression varied from a nuclear location (sun-exposed skin) to a cytoplasmic location (cSCC). Western blot analyses confirmed the enhancement of FOSL1 and BNC1 expression. Additionally, the smallest overlapping regions of genomic imbalance (SORIs) involving at least 3 of the samples of each group (sun-exposed skin, AK or cSCC) were selected. One of the SORIs was a deletion in the p24.1 band of chromosome 3, shared by 7 of the cSCC. A strong correlation in the integration analysis was found for NEK10, a gene contained in the previously mentioned SORI. Loss of NEK10 expression in cSCC was confirmed by immunohistochemistry and western blot analyses. In conclusion, our findings suggest that FOSL1 may play a role in promoting the cSCC invasion ability. We have also identified two additional genes, NEK10 and BNC1, which could also act as tumor drivers.
Transcriptome and cytogenetic profiling analysis of matched in situ/invasive cutaneous squamous cell carcinomas from immunocompetent patients.
Sex, Age, Specimen part, Disease stage, Subject
View SamplesIn this data, we examined Transcriptome detection and expression in 8 samples of Retinoblastoma. We found a central core shared by all samples .
Discovery of a transcriptomic core of genes shared in 8 primary retinoblastoma with a novel detection score analysis.
Disease
View SamplesBackground and Purpose
Upregulated signaling pathways in ruptured human saccular intracranial aneurysm wall: an emerging regulative role of Toll-like receptor signaling and nuclear factor-κB, hypoxia-inducible factor-1A, and ETS transcription factors.
No sample metadata fields
View SamplesCutaneous squamous cell carcinoma (cSCC) is the second most common malignancy in humans and approximately 5% metastasize, usually to regional lymph nodes. Epigenetic regulation of gene expression may allow tumoral cells to acquire new functions in order to escape from the primary tumor. The aim of this study was to investigate the expression and function of proteins of the Polycomb family of epigenetic regulators in the metastatic process of cSCC. A higher expression of RING1B and EZH2 was detected by immunohistochemistry in a series of primary cSCC tumors that metastasized (MSCC) when compared to non metastasizing cSCC (non MSCC). Stable downregulation of RING1B and EZH2 in cSCC cells results in enhanced expression of inflammatory cytokines and activation of the NFB signaling pathway. Accordingly, non MSCC display higher levels of membranous pS176 IKK and their stroma is enriched in neutrophils and eosinophils when compared to MSCC. In vitro, hematopoietic cells exhibit a substantial migratory response to supernatants from Polycomb depleted cSCC cells. Altogether these data indicate that RING1B and EZH2 repress the innate inflammatory cSCC function and impair tumor immunosurveillance and suggest that patients with high risk cSCC could benefit from clinical therapies addressed to harness the immune response.
The Polycomb proteins RING1B and EZH2 repress the tumoral pro-inflammatory function in metastasizing primary cutaneous squamous cell carcinoma.
Specimen part, Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Immunopathology of childhood celiac disease-Key role of intestinal epithelial cells.
Specimen part, Cell line, Treatment
View SamplesAnalysis of the influence of celiac disease-associated bacteria and gluten on intestinal epithelial cells
Immunopathology of childhood celiac disease-Key role of intestinal epithelial cells.
Cell line, Treatment
View SamplesAnalysis of the influence of celiac disease-associated bacteria and gluten on intestinal epithelial cells
Immunopathology of childhood celiac disease-Key role of intestinal epithelial cells.
Cell line, Treatment
View Samples