We disprove that the impaired Myd88-dependent proinflammatory response of neonatal monocytes is a correlate for immaturity and confirm it as display of transient alarmin-mediated stress tolerization. We find a strong inducibility of TRIF-dependent genes in neonatal monocytes by LPS but a barely detectable expression at baseline.
S100-alarmin-induced innate immune programming protects newborn infants from sepsis.
Specimen part, Treatment
View SamplesTofacitinib is an oral Janus kinase inhibitor being investigated for psoriasis. We sought to elucidate the molecular mechanisms underlying the clinical efficacy of tofacitinib in patients with psoriasis. Twelve patients with plaque psoriasis were randomized (3:1) to receive 10mg of tofacitinib or placebo twice daily for 12weeks. Biopsy specimens were taken from nonlesional (baseline) and lesional (baseline, days 1 and 3, and weeks 1, 2, 4, and 12) skin. Biopsy specimens were examined for psoriatic epidermal features (thickness, Ki67+ keratinocytes and keratin 16 [KRT16] mRNA expression, and phosphorylated signal transducer and activator of transcription [pSTAT]+ nuclei) and T-cell and dendritic cell (DC) subsets by using immunohistochemistry, and mRNA transcripts were quantified by using a microarray. In lesional skin keratinocyte pSTAT1 and pSTAT3 staining was increased at baseline but reduced after 1day of tofacitinib (baseline, median of 1290 pSTAT1+ cells/?m2; day 1, median of 332 pSTAT1+ cells/?m2; and nonlesional, median of 155 pSTAT1+ cells/?m2). Epidermal thickness and KRT16 mRNA expression were significantly and progressively reduced after days 1 and 3 of tofacitinib administration, respectively (eg, KRT16 decreased 2.74-fold, day 3 vs baseline, P=.016). Decreases in DC and T-cell numbers were observed after weeks 1 and 2, respectively. At week 4, significant decreases in IL-23/TH17 pathways were observed that persisted through week 12. Improvements in clinical and histologic features were strongly associated with changes in expression of psoriasis-related genes and reduction in IL-17 gene expression. Tofacitinib has a multitiered response in patients with psoriasis: (1) rapid attenuation of keratinocyte Janus kinase/STAT signaling; (2) removal of keratinocyte-induced cytokine signaling, leading to reductions in pathologic DC andT-cell numbers to nonlesional levels; and (3) inhibition of the IL-23/TH17 pathway.
Tofacitinib attenuates pathologic immune pathways in patients with psoriasis: A randomized phase 2 study.
Specimen part, Disease, Treatment, Subject, Time
View SamplesTo compare human memory CD4+ T cell subsets in peripheral blood (PB) and bone marrow (BM) of healthy individuals at transcriptional level, we analyzed the global gene expression of ex vivo PB CD69- as well as BM CD69- and CD69+ memory CD4+ T cells from 4 paired PB and BM samples. The gene expression of these subsets was additionally compared to the transcriptional profile of 8 PB samples taken ex vivo or stimulated with phorbol myristate acetate (PMA) and Ionomycin for 3 hours.
Human memory T cells from the bone marrow are resting and maintain long-lasting systemic memory.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Polarization of the effects of autoimmune and neurodegenerative risk alleles in leukocytes.
Sex, Age, Specimen part
View SamplesGene expression profiling of CD4 T-Cells (CD4+CD62L+) from human peripheral blood mononuclear cells (PBMCs). PBMCs were isolated from healthy individuals from the Boston area.
Polarization of the effects of autoimmune and neurodegenerative risk alleles in leukocytes.
Sex, Age, Specimen part
View SamplesGene expression profiling of Monocytes (CD14+CD16-) from human peripheral blood mononuclear cells (PBMCs). PBMCs were isolated from healthy individuals from the Boston area.
Polarization of the effects of autoimmune and neurodegenerative risk alleles in leukocytes.
Sex, Specimen part
View SamplesAnalysis of biopsy hippocampal tissue of patients with pharmacoresistant temporal lobe epilepsy (TLE) undergoing neurosurgical removal of the epileptogenic focus for seizure control. Chronic TLE goes along with focal hyperexcitability. Results provide insight into molecular mechanisms that may play a role in seizure propensity
Systems genetics identifies Sestrin 3 as a regulator of a proconvulsant gene network in human epileptic hippocampus.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Integration of transcript expression, copy number and LOH analysis of infiltrating ductal carcinoma of the breast.
Specimen part, Subject
View SamplesIntroduction: A major challenge in the interpretation of genomic profiling data generated from breast cancer samples is the identification of driver genes as distinct from bystander genes which do not impact tumorigenesis. One way to assess the relative importance of alterations in the transcriptome profile is to combine complementary analyses that assess changes in the copy number alterations (CNAs). This integrated analysis permits the identification of genes with altered expression that map within specific chromosomal regions that demonstrate copy number alterations, providing a mechanistic approach to identify the 'driver genes.
Integration of transcript expression, copy number and LOH analysis of infiltrating ductal carcinoma of the breast.
Specimen part, Subject
View SamplesTranscriptome analysis of LDBM cells stimulated with IL-5
IL-5 triggers a cooperative cytokine network that promotes eosinophil precursor maturation.
Specimen part
View Samples