Similar Datasets
Project description:Colonic Rorgt+Foxp3+ Treg cells are critical to maintain intestinal homeostasis and prevent inflammatory bowel diseases by suppressing exuberant innate and adaptative immune responses. In this study, In this study, we found that REV-ERB was highly expressed in colonic RORt+Foxp3+ Treg cells and essential for their differentiation and function. Deletion of REV-ERB in Treg cells lead to diminished colonic RORt+Foxp3+ Treg cell populations even at steady state, and render mice more susceptible to TNBS and/or oxazolone-induced colitis. As a transcriptional repressor, REV-ERB can directly repress the expression of pro-inflammatory cytokines IL-17a and IL-17f, and promote RORt expression through Bhlhe40-c-maf axis in RORt+Foxp3+ Treg cells. Furthermore, REV-ERB also orchestrate RORt genome-wide distributions and co-regulate core signature genes in RORt+Foxp3+ Treg cells, including IL-10, CTLA-4, Icos, c-maf.
2025-11-10 | GSE225202 | GEO
Project description:Colonic Rorgt+Foxp3+ Treg cells are critical to maintain intestinal homeostasis and prevent inflammatory bowel diseases by suppressing exuberant innate and adaptative immune responses. In this study, In this study, we found that REV-ERBa was highly expressed in colonic RORgt+Foxp3+ Treg cells and essential for their differentiation and function. Deletion of REV-ERB in Treg cells lead to diminished colonic RORgt+Foxp3+ Treg cell populations even at steady state, and render mice more susceptible to TNBS and/or oxazolone-induced colitis. As a transcriptional repressor, REV-ERBa can directly repress the expression of pro-inflammatory cytokines IL-17a and IL-17f, and promote RORgt expression through Bhlhe40-c-maf axis in RORgt+Foxp3+ Treg cells. Furthermore, REV-ERB also orchestrate RORgt genome-wide distributions and co-regulate core signature genes in RORgt+Foxp3+ Treg cells, including IL-10, CTLA-4, Icos, c-maf.
2025-11-10 | GSE225200 | GEO
Project description:REV-ERBα regulates regulatory T cell function in inflammatory bowel disease
| PRJNA934326 | ENA
Project description:REV-ERBα regulates regulatory T cell function in inflammatory bowel disease [CUT&RUN]
| PRJNA934503 | ENA
Project description:REV-ERBα regulates regulatory T cell function in inflammatory bowel disease [RNA-seq]
| PRJNA934504 | ENA
Project description:Circadian dysfunction is a common attribute of many neurodegenerative diseases, most of which are associated with neuroinflammation. Circadian rhythm dysfunction has been associated with inflammation in the periphery, but the role of the core clock in neuroinflammation remains poorly understood. Here we demonstrate that Rev-erbα, a nuclear receptor and circadian clock component, is a mediator of microglial activation and neuroinflammation. We observed time-of-day oscillation in microglial immunoreactivity in the hippocampus, which was disrupted in Rev-erbα-/- mice. Rev-erbα deletion caused spontaneous microglial activation in the hippocampus and increased expression of proinflammatory transcripts, as well as secondary astrogliosis. Transcriptomic analysis of hippocampus from Rev-erbα-/- mice revealed a predominant inflammatory phenotype and suggested dysregulated NF-κB signaling. Primary Rev-erbα-/- microglia exhibited proinflammatory phenotypes and increased basal NF-κB activation. Chromatin immunoprecipitation revealed that Rev-erbα physically interacts with the promoter regions of several NF-κB-related genes in primary microglia. Loss of Rev-erbα in primary astrocytes had no effect on basal activation but did potentiate the inflammatory response to lipopolysaccharide (LPS). In vivo, Rev-erbα-/- mice exhibited enhanced hippocampal neuroinflammatory responses to peripheral LPS injection, while pharmacologic activation of Rev-erbs with the small molecule agonist SR9009 suppressed LPS-induced hippocampal neuroinflammation. Rev-erbα deletion influenced neuronal health, as conditioned media from Rev-erbα-deficient primary glial cultures exacerbated oxidative damage in cultured neurons. Rev-erbα-/- mice also exhibited significantly altered cortical resting-state functional connectivity, similar to that observed in neurodegenerative models. Our results reveal Rev-erbα as a pharmacologically accessible link between the circadian clock and neuroinflammation.
| S-EPMC6421453 | biostudies-literature
Project description:The circadian clock regulates behavioural and physiological processes in a 24-h cycle. The nuclear receptors REV-ERBα and REV-ERBβ are involved in the cell-autonomous circadian transcriptional/translational feedback loops as transcriptional repressors. A number of studies have also demonstrated a pivotal role of REV-ERBs in regulation of metabolic, neuronal, and inflammatory functions including bile acid metabolism, lipid metabolism, and production of inflammatory cytokines. Given the multifunctional role of REV-ERBs, it is important to elucidate the mechanism through which REV-ERBs exert their functions. To this end, we established a Rev-erbα/Rev-erbβ double-knockout mouse embryonic stem (ES) cell model and analyzed the circadian clock and clock-controlled output gene expressions. A comprehensive mRNA-seq analysis revealed that the double knockout of both Rev-erbα and Rev-erbβ does not abrogate expression rhythms of E-box-regulated core clock genes but drastically changes a diverse set of other rhythmically-expressed output genes. Of note, REV-ERBα/β deficiency does not compromise circadian expression rhythms of PER2, while REV-ERB target genes, Bmal1 and Npas2, are significantly upregulated. This study highlight the relevance of REV-ERBs as pivotal output mediators of the mammalian circadian clock.
| S-EPMC6629614 | biostudies-literature
Project description:Brown adipose tissue is a major thermogenic organ that plays a key role in maintenance of body temperature and whole-body energy homeostasis. Rev-erbα, a ligand-dependent nuclear receptor and transcription repressor of the molecular clock, has been implicated in the regulation of adipogenesis. However, whether Rev-erbα participates in brown fat formation is not known. Here we show that Rev-erbα is a key regulator of brown adipose tissue development by promoting brown adipogenesis. Genetic ablation of Rev-erbα in mice severely impairs embryonic and neonatal brown fat formation accompanied by loss of brown identity. This defect is due to a cell-autonomous function of Rev-erbα in brown adipocyte lineage commitment and terminal differentiation, as demonstrated by genetic loss- and gain-of-function studies in mesenchymal precursors and brown preadipocytes. Moreover, pharmacological activation of Rev-erbα activity promotes, whereas its inhibition suppresses brown adipocyte differentiation. Mechanistic investigations reveal that Rev-erbα represses key components of the TGF-β cascade, an inhibitory pathway of brown fat development. Collectively, our findings delineate a novel role of Rev-erbα in driving brown adipocyte development, and provide experimental evidence that pharmacological interventions of Rev-erbα may offer new avenues for the treatment of obesity and related metabolic disorders.
| S-EPMC4462032 | biostudies-literature
Project description:The nuclear receptor Rev-erbα regulates circadian rhythm and metabolism, but its effects are modest and it has been considered to be a secondary regulator of the cell-autonomous clock. Here we report that depletion of Rev-erbα together with closely related Rev-erbβ has dramatic effects on the cell-autonomous clock as well as hepatic lipid metabolism. Mouse embryonic fibroblasts were rendered arrhythmic by depletion of both Rev-erbs. In mouse livers, Rev-erbβ mRNA and protein levels oscillate with a diurnal pattern similar to that of Rev-erbα, and both Rev-erbs are recruited to a remarkably similar set of binding sites across the genome, enriched near metabolic genes. Depletion of both Rev-erbs in liver synergistically derepresses several metabolic genes as well as genes that control the positive limb of the molecular clock. Moreover, deficiency of both Rev-erbs causes marked hepatic steatosis, in contrast to relatively subtle changes upon loss of either subtype alone. These findings establish the two Rev-erbs as major regulators of both clock function and metabolism, displaying a level of subtype collaboration that is unusual among nuclear receptors but common among core clock proteins, protecting the organism from major perturbations in circadian and metabolic physiology.
| S-EPMC3323877 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2021-03-31 | GSE171190 | GEO