This SuperSeries is composed of the SubSeries listed below.
Transcriptional analysis of HIV-specific CD8+ T cells shows that PD-1 inhibits T cell function by upregulating BATF.
Specimen part
View SamplesCD8+ T cells in chronic viral infections like HIV develop functional defects such as loss of IL-2 secretion and decreased proliferative potential that are collectively termed exhaustion1. Exhausted T cells express increased levels of multiple inhibitory receptors, such as Programmed Death 1 (PD-1). PD-1 inhibition contributes to impaired virus-specific T cell function in chronic infection because antibody-mediated blockade of its ligand, Programmed Death Ligand 1 (PD-L1) is sufficient to improve T cell function and reduce viral replication in animal models. Reversing PD-1 inhibition is therefore an attractive therapeutic target, but the cellular mechanisms by which PD-1 ligation results in T cell inhibition are not fully understood. PD-1 is thought to limit T cell activation by attenuating T cell receptor (TCR) signaling. It is not known whether PD-1 ligation also acts by upregulating genes in exhausted T cells that impair their function. Here, we analyzed gene-expression profiles from HIV-specific CD8+ T cells in patients with HIV and show that PD-1 coordinately upregulates a program of genes in exhausted CD8+ T cells from humans and mice. This program includes upregulation of basic leucine transcription factor, ATF-like (BATF), a transcription factor in the AP-1 family. Enforced expression of BATF was sufficient to impair T cell proliferation and cytokine secretion, while BATF knockdown reduced PD-1 inhibition. Silencing BATF in CD4+ and CD8+ T cells from chronic viremic patients rescued HIV-specific T cell function. Thus inhibitory receptors can cause T cell exhaustion by upregulating genes such as BATF that inhibit T cell function.
Transcriptional analysis of HIV-specific CD8+ T cells shows that PD-1 inhibits T cell function by upregulating BATF.
Specimen part
View SamplesCD8+ T cells in chronic viral infections like HIV develop functional defects such as loss of IL-2 secretion and decreased proliferative potential that are collectively termed exhaustion1. Exhausted T cells express increased levels of multiple inhibitory receptors, such as Programmed Death 1 (PD-1). PD-1 inhibition contributes to impaired virus-specific T cell function in chronic infection because antibody-mediated blockade of its ligand, Programmed Death Ligand 1 (PD-L1) is sufficient to improve T cell function and reduce viral replication in animal models. Reversing PD-1 inhibition is therefore an attractive therapeutic target, but the cellular mechanisms by which PD-1 ligation results in T cell inhibition are not fully understood. PD-1 is thought to limit T cell activation by attenuating T cell receptor (TCR) signaling. It is not known whether PD-1 ligation also acts by upregulating genes in exhausted T cells that impair their function. Here, we analyzed gene-expression profiles from HIV-specific CD8+ T cells in patients with HIV and show that PD-1 coordinately upregulates a program of genes in exhausted CD8+ T cells from humans and mice. This program includes upregulation of basic leucine transcription factor, ATF-like (BATF), a transcription factor in the AP-1 family. Enforced expression of BATF was sufficient to impair T cell proliferation and cytokine secretion, while BATF knockdown reduced PD-1 inhibition. Silencing BATF in CD4+ and CD8+ T cells from chronic viremic patients rescued HIV-specific T cell function. Thus inhibitory receptors can cause T cell exhaustion by upregulating genes such as BATF that inhibit T cell function.
Transcriptional analysis of HIV-specific CD8+ T cells shows that PD-1 inhibits T cell function by upregulating BATF.
Specimen part
View SamplesBiomarkers of osteoarthritis (OA) that can accurately diagnose the disease at the earliest stage would significantly support efforts to develop treatments for prevention and early intervention. The different stages of disease progression are described by the complex pattern of transcriptional regulations. The dynamics in pattern alterations were monitored in each individual animal during the time-course of OA progression.
Blood Transcriptional Signatures for Disease Progression in a Rat Model of Osteoarthritis.
Treatment
View SamplesDifferences between groups of children with obesity and healthy controls.
Looking for new diagnostic tools and biomarkers of hypertension in obese pediatric patients.
Specimen part, Disease
View SamplesChronic opiate use produces molecular and cellular adaptations in the nervous system, leading to tolerance, physical dependence and addiction. Genome-wide comparison of morphine-induced changes in brain transcription of mouse strains with different opioid-related phenotypes provides an opportunity to discover the relationship between gene expression and behavioral response to the drug.
Morphine effects on striatal transcriptome in mice.
No sample metadata fields
View SamplesTo identify molecular effects of chronic drug treatment, heroin and methamphetamine treated animals were compared with saline treated animals at multiple time-points using microarray technology. Gene expression profile was assessed 14 h after the last dose of 1, 3, 6 or 12 days drug treatment and after 13, 15, 18 or 24 days of withdrawal.
Common transcriptional effects in the mouse striatum following chronic treatment with heroin and methamphetamine.
Specimen part, Compound
View SamplesChronic exposure to opioids induces adaptations in brain function that lead to the formation of the behavioral and physiological symptoms of drug dependence and addiction.
Behavioral and transcriptional patterns of protracted opioid self-administration in mice.
Specimen part
View SamplesWe used the CRISPR/Cas9 technique to construct nbr1-KO lines (KO1 and KO3) in order to test the effects of AtNBR1 depletion. Reduced expression of several ABA-up regulated genes were observed in shoots of the two KO lines.
A selective autophagy cargo receptor NBR1 modulates abscisic acid signalling in Arabidopsis thaliana.
Age, Specimen part
View SamplesAblation of the Srf gene in dopaminoceptive neurons of the brain was performed using the Cre/loxP system, with the recombinase expressed from a BAC-derived Drd1a promoter.
Loss of the serum response factor in the dopamine system leads to hyperactivity.
No sample metadata fields
View Samples