Given their precipitous encounter with the environment, newborn infants might be expected to possess abundant immunoprotective mechanisms. Paradoxically, their T cells display grossly impaired Th1 anti-bacterial and anti-viral responses. This study identifies factors produced by neonatal CD4 T cells when compared with adult naive CD4 T cells and highlights CXCL8 as a pivotal effector molecule in neonatal T cells. Using Affimetrix microarray we compared gene expression in cord blood derived CD4 T cells with naive CD4 T cells from adults after polyclonal stimulation.
Interleukin-8 (CXCL8) production is a signatory T cell effector function of human newborn infants.
Specimen part
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Expression quantitative trait loci mapping identifies new genetic models of glutathione S-transferase variation.
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View SamplesAn unanticipated feature of the human neonatal CD4 T cell response is a robust capacity to produce CXCL8. However, this ''innate-like'' function dissipates with age and is scarce in the adult. Here, we investigated the fate of CD4+CXCL8+ cells and their transition into conventional adaptive T cells. We show that CXCL8 is imprinted on immature thymocytes prior to TCR signalling and is maintained in T cell committed thymic progenitors and recent thymic emigrants (RTEs) of adults as well as neonates. Hence, rather than being unique to neonates, CXCL8-producing CD4+ T cells decrease with age in humans (and in humanised mice) owing to the decline in thymic output, coupled with the cells' peripheral expansion. By cloning of CXCL8+CD4+ cells from cord blood, we were able to track effector function within daughter cells and demonstrate that these cells can convert to IFN-g producing cells. In sum, we provide direct evidence that 'innate like' CXCL8-producing CD4+ T cells emerge from the thymus and can transition into conventional adaptive Th1 cells Overall design: Examination of RNA-Seq count data from 96 single cells
Adaptive from Innate: Human IFN-γ<sup>+</sup>CD4<sup>+</sup> T Cells Can Arise Directly from CXCL8-Producing Recent Thymic Emigrants in Babies and Adults.
Specimen part, Subject
View SamplesRationale: Obstructive sleep apnea (OSA) has been associated with metabolic dysregulation and systemic inflammation. This may be due to pathophysiologic effects of OSA on visceral adipose tissue. We sought to assess the transcriptional consequences of OSA on adipocytes by utilizing pathway-focused analyses.
A pathway-based analysis on the effects of obstructive sleep apnea in modulating visceral fat transcriptome.
Subject
View SamplesAeromonas caviae has been associated with human gastrointestinal disease. Strains of this species typically lack virulence factors (VFs) such as enterotoxins and hemolysins that are produced by other human pathogens of the Aeromonas genus. Microarray profiling of murine small intestinal extracts, 24 hours after oral infection with an A. caviae strain, provides evidence of a Th1 type immune response. A large number of gamma-interferon (-IFN) induced genes are up-regulated as well as several tumor necrosis factor-alpha (TNF-) transcripts. A. caviae has always been considered an opportunistic pathogen because it lacks obvious virulence factors. This current effort suggests A. caviae colonizes murine intestinal tract and causes what has been described by others as a dysregulatory cytokine response leading to an irritable bowel-like syndrome. This response would explain why a number of diarrheal waterborne outbreaks have been attributed to A. caviae even though it lacks obvious enteropathogenic properties.
Aeromonas caviae strain induces Th1 cytokine response in mouse intestinal tract.
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View SamplesA gene expression profiling sub-study was conducted in which skin biopsy samples were collected from 85 patients with moderate-to-severe psoriasis who were participating in ACCEPT, an IRB-approved Phase 3, multicenter, randomized trial. This analysis identified 4,175 probe-sets as being significantly modulated in psoriasis lesions (LS) compared with matched biopsies of non-lesional (NL) skin.
Expanding the psoriasis disease profile: interrogation of the skin and serum of patients with moderate-to-severe psoriasis.
Specimen part, Disease, Disease stage, Subject
View SamplesRationale: Obstructive sleep apnea (OSA) has been associated with a number of chronic disorders that may improve with effective therapy. However, the molecular pathways affected by continuous positive airway pressure (CPAP) treatment are largely unknown. We sought to assess the system-wide consequences of CPAP therapy by transcriptionally profiling peripheral blood leukocytes (PBLs). Methods: Subjects diagnosed with severe OSA were treated with CPAP, and whole-genome expression measurement of PBLs was performed at baseline and following therapy. We used Gene Set Enrichment Analysis (GSEA) to identify gene sets that were differentially enriched. Network analysis was then applied to identify key drivers of pathways influenced by CPAP. Results: 18 subjects with severe OSA (apnea hypopnea index 30 events/hour) underwent CPAP therapy and microarray analysis of their PBLs. Treatment with CPAP improved AHI, daytime sleepiness and blood pressure but did not affect anthropometric measures. GSEA revealed a number of enriched gene sets, many of which were involved in neoplastic processes and displayed down-regulated expression patterns in response to CPAP. Network analysis identified several densely connected genes that are important modulators of cancer and tumor growth. Conclusions: Effective therapy of OSA with CPAP is associated with alterations in circulating leukocyte gene expression. Functional enrichment and network analyses highlighted transcriptional suppression in cancer-related pathways suggesting potentially novel mechanisms linking OSA with neoplastic signatures.
Treatment of obstructive sleep apnea alters cancer-associated transcriptional signatures in circulating leukocytes.
Treatment, Subject
View SamplesA study of diabetic neuropathy in dorsal root ganglia from streptozotocin-diabetic male wistar rats over the first 8 weeks of diabetes
Identification of changes in gene expression in dorsal root ganglia in diabetic neuropathy: correlation with functional deficits.
Sex, Age, Specimen part, Disease, Disease stage, Time
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Drosophila larvae fed palm fruit juice (PFJ) delay pupation via expression regulation of hormetic stress response genes linked to ageing and longevity.
Age, Specimen part, Treatment
View SamplesPFJ (4 ml for a final concentration of 19,000 mg gallic acid equivalent (GAE) per kg diet or 0.86 mg GAE per kcal diet) was supplemented to larvae of fruit flies (Drosophila melanogaster) given a semi-purified diet to observe for possible effects on energy metabolism and lifespan. Larvae were used five days since the egg stage for gene expression studies. Results from the microarray data analysis carried out show that fruit fly larvae given PFJ had up-regulated transport and metabolic processes, while development and morphogenesis processes were down-regulated.
Drosophila larvae fed palm fruit juice (PFJ) delay pupation via expression regulation of hormetic stress response genes linked to ageing and longevity.
Age, Specimen part, Treatment
View Samples