The inhibitory receptor Tim-3 has emerged as a critical regulator of the T cell dysfunction that develops in chronic viral infections and cancers. However, little is known regarding the signaling pathways that drive Tim-3 expression. Here, we demonstrate that IL-27 induces NFIL3, which promotes permissive chromatin remodeling of the Tim-3 locus and induces Tim-3 expression together with the immunosuppressive cytokine IL-10. We further show that the IL-27/NFIL3 signaling axis is crucial for the induction of Tim-3 in vivo. IL-27-conditioned Th1 cells exhibit reduced effector function and are poor mediators of intestinal inflammation. This inhibitory effect is NFIL3 dependent. In contrast, tumor-infiltrating lymphocytes (TILs) from IL-27R-/- mice exhibit reduced NFIL3, less Tim-3 expression and failure to develop dysfunctional phenotype, resulting in better tumor growth control. Thus, our data identify an IL-27/NFIL3 signaling axis as a key regulator of effector T cell responses via induction of Tim-3, IL-10, and T cell dysfunction.
An IL-27/NFIL3 signalling axis drives Tim-3 and IL-10 expression and T-cell dysfunction.
Sex, Specimen part
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Mechanistic Differences in Neuropathic Pain Modalities Revealed by Correlating Behavior with Global Expression Profiling.
Sex, Specimen part, Treatment
View SamplesChronic neuropathic pain is a major morbidity of neural injury, yet its mechanisms are incompletely understood. Hypersensitivity to previously non-noxious stimuli (allodynia) is a common symptom. Here, we demonstrate that the onset of cold hypersensitivity precedes tactile allodynia and this temporal divergence was associated with major differences in global gene expression in dorsal root ganglia. Transcripts whose expression correlate with the onset of cold allodynia were nociceptor-related whereas those correlating with tactile hypersensitivity were enriched for immune cell activity. Selective ablation of TrpV1 lineage nociceptors resulted in mice that did not acquire cold allodynia but developed normal tactile hypersensitivity. Whereas depletion of macrophages or T cells reduced neuropathic tactile allodynia but not cold hypersensitivity. We conclude that neuropathic pain is contributed to by reactive processes of sensory neurons and immune cells, each leading to distinct forms of pain hypersensitivity, potentially allowing effective drug development targeted to each pain modality. Overall design: High temporal analysis of global gene expression in the DRG following spared nerve injury (SNI) correlated with behavior taken at the same time points. Expression and behavioral sensitivity taken at least daily over the first 10 days post SNI.
Mechanistic Differences in Neuropathic Pain Modalities Revealed by Correlating Behavior with Global Expression Profiling.
Sex, Specimen part, Cell line, Subject
View SamplesChronic neuropathic pain is a major morbidity of neural injury, yet its mechanisms are incompletely understood. Hypersensitivity to previously non-noxious stimuli (allodynia) is a common symptom. Here, we demonstrate that the onset of cold hypersensitivity precedes tactile allodynia and this temporal divergence was associated with major differences in global gene expression in dorsal root ganglia (DRG). Transcripts whose expression correlate with the onset of cold allodynia were nociceptor-related, whereas those correlating with tactile hypersensitivity were enriched for immune cell activity. Selective ablation of TrpV1 lineage nociceptors resulted in mice that did not acquire cold allodynia but developed normal tactile hypersensitivity. Whereas, depletion of macrophages or T cells reduced neuropathic tactile allodynia but not cold hypersensitivity. We conclude that neuropathic pain is contributed to by reactive processes of sensory neurons and immune cells, each leading to distinct forms of pain hypersensitivity, potentially allowing effective drug development targeted to each pain modality.
Mechanistic Differences in Neuropathic Pain Modalities Revealed by Correlating Behavior with Global Expression Profiling.
Sex, Specimen part, Treatment
View SamplesWe hypothesize that gene expression in the CS-exposed lungs of this strain (A/J) of mice would be able to give clues about the molecular mechanism of emphysema development, thus contributing to this phenotype. More specifically, although imbalance in oxidants/antioxidants and proteinase/antiproteinase pathways drives the pathogenesis of COPD, the molecular mechanisms involved in the development of emphysema are poorly understood. In order to test this hypothesis at the gene expression level, we utilized microarray analysis to examine transcriptional differences between CS-exposed and Air-exposed groups of mice.
Cigarette smoke-induced emphysema in A/J mice is associated with pulmonary oxidative stress, apoptosis of lung cells, and global alterations in gene expression.
Sex, Age, Specimen part
View SamplesWe hypothesize that gene expression in the cigarette smoke (CS) exposed neonatal lung and age-matched controls will be divergent. CS exposed lung will have divergence of immune response genes and structural genes. The lungs of (6) 2 week old neonatal mice exposed to 2 weeks of CS were compared to the lung of (4) 2 week old age-matched control mice. We utilized microarray analysis to examine transcriptional differences between smoke exposed neonatal lung and age-matched controls.
Impaired lung homeostasis in neonatal mice exposed to cigarette smoke.
No sample metadata fields
View SamplesThis experiment was conducted to test multiple hypotheses: 1) long-wave 365 nm UV light exposure at low fluences does not alter gene expression of hMSC, 2) presence of radical species during polymerization causes DNA damage in hMSC, 3) 3D encapsulation of hMSC causes changes in gene expression of hMSC compared with traditional 2D culture, 4) Differencesin 3D hydrogel networks induce gene expression changes in hMSC
Low-Dose, Long-Wave UV Light Does Not Affect Gene Expression of Human Mesenchymal Stem Cells.
Specimen part
View SamplesThree groups of male +b and bb rats were obtained (ages between 6 and 14 months) and intestinal scrapes were taken. Tissues was combined from 3 rats per group and processed for gene chip analysis.
Induction of arachidonate 12-lipoxygenase (Alox15) in intestine of iron-deficient rats correlates with the production of biologically active lipid mediators.
No sample metadata fields
View SamplesTo study effects of IFNalpha treatment on monocyte-derived macrophages which may influence susceptibility or resistance to HIV.
Interleukin-27 inhibition of HIV-1 involves an intermediate induction of type I interferon.
Specimen part
View SamplesTo investigate the role of RAD21 in the transcriptional regulation of global gene expression at early stage of colorectal cancer developments, we peformed the genome-wide analysis to map genomic regions bound by Rad21 in normal small testinal crypts and tumors (adenomas) harvested from Apc Min/+ mice using ChIP-seq. ChIP-seq naalysis identified high confidence RAD21 binding sites unique to normal crypts or adenomas, as well as those common to both tissues. We further performed RNA-seq to profile the changes in gene expression from normal WT crypts to adenomas at the very early stage of adenomagenesis in the context of Rad21 heterozygous loss. Overall design: mRNA profiles of normal small intestinal crypts (WT) and adenomas from Apc Min/+ and Apc Min/+:Rad21+/- double mutant mouse; Mapping of Rad21 genomic binding sites in normal intestinal crypts (WT) and Apc Min/+ adenomas
Cohesin Rad21 mediates loss of heterozygosity and is upregulated via Wnt promoting transcriptional dysregulation in gastrointestinal tumors.
No sample metadata fields
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