Role of RelB in Interferon Dependent and Indpendent Gene Regulation
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE224515 | GEO | 2023/02/06
REPOSITORIES: GEO
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Project description:Thymic medullary epithelial cell (mTEC) expression of the autoimmune regulator AIRE, and of tissue-specific antigens, is controlled by members of the non-canonical NF-kB signalling pathway, including RelB and NF-kB2. Of the genes in this pathway, RelB-/- mice develop a particularly severe multi-organ autoimmune syndrome, resembling Foxp3-deficiency. RelB-/- mice have medullary atrophy and few mTECs but the mechanism is unknown. We show that RelB is required for expression of medullary chemokines and mTEC AIRE, selection of a diverse peripheral T cell repertoire, and for peripheral Foxp3+ Treg function. Vβ families of T cells infiltrating diseased peripheral organs and thymic Treg were similarly skewed. Surprisingly, medullary atrophy results from intra-thymic granulocyte infiltration, consequent upon the Th2-mediated autoimmune disease. Dominant tolerance corrects thymic inflammatory disease and loss of thymic function. We demonstrate a reversible RelB-dependent inflammatory mechanism for loss of central tolerance associated with medullary atrophy. Thymi from 4 RelB+/- mice and 3 RelB-/- mice were profiled by microarays
2012-12-27 | E-GEOD-43154 | biostudies-arrayexpress
Project description:Thymic medullary epithelial cell (mTEC) expression of the autoimmune regulator AIRE, and of tissue-specific antigens, is controlled by members of the non-canonical NF-kB signalling pathway, including RelB and NF-kB2. Of the genes in this pathway, RelB-/- mice develop a particularly severe multi-organ autoimmune syndrome, resembling Foxp3-deficiency. RelB-/- mice have medullary atrophy and few mTECs but the mechanism is unknown. We show that RelB is required for expression of medullary chemokines and mTEC AIRE, selection of a diverse peripheral T cell repertoire, and for peripheral Foxp3+ Treg function. Vβ families of T cells infiltrating diseased peripheral organs and thymic Treg were similarly skewed. Surprisingly, medullary atrophy results from intra-thymic granulocyte infiltration, consequent upon the Th2-mediated autoimmune disease. Dominant tolerance corrects thymic inflammatory disease and loss of thymic function. We demonstrate a reversible RelB-dependent inflammatory mechanism for loss of central tolerance associated with medullary atrophy.
2012-12-27 | GSE43154 | GEO
Project description:Role of RelB in Interferon Dependent and Indpendent Gene Regulation
| PRJNA931364 | ENA
Project description:Dysfunction of the non-canonical NF-kB signaling pathway has been causally associated with numbers of cancers and autoimmune diseases. However, specific inhibitors for this signaling pathway remain to be developed. Here we showed that structure-based cell-based screening yielded a potent and specific small molecule targeting RelB to inhibit non-canonical NF-kB signaling pathway, while had no inhibitory effect on canonical NF-kB signaling pathway. Mechanistically, the inhibitor directly interacted with RelB protein and disrupted RelB binding to its target DNA, thus repressing RelB transactivity on target genes. Through blocking oncogenic activity of non-canonical NF-kB signaling pathway in colorectal cancer or B lymphoma, the inhibitor efficiently exerted a potent antitumor effect in vitro and in vivo. Thus, our study provided new RelB-targeting inhibitor that inhibited non-canonical NF-kB signaling pathway and facilitated precise therapeutic applications in cancers and possibly other diseases.
2025-04-23 | GSE288086 | GEO
Project description:Background: Lymphotoxin signaling via the lymphotoxin-β receptor (LTβR) has been implicated in several biological processes, ranging from development of secondary lymphoid organs, maintenance of splenic tissue, host defense against pathogens, autoimmunity, and lipid homeostasis. The major transcription factor that is activated by LTβR crosslinking is NF-κB. Two signaling pathways have been described that result in the activation of classical p50-RelA and alternative p52-RelB NF-κB heterodimers. Results: Using microarray analysis, we investigated the transcriptional response downstream of the LTβR in mouse embryoni fibroblasts (MEF) and its regulation by the RelA and RelB subunits of NF-κB. We describe novel LTβR-responsive genes that are regulated by RelA and/or RelB. Interestingly, we found that the majority of LTβR-regulated genes require the presence of both RelA and RelB, suggesting significant crosstalk between the two NF-κB activation pathways. Gene Ontology (GO) analysis confirmed that LTβR-NF-κB target genes are predominantly involved in the regulation of immune responses. However, other biological processes, such as apoptosis/cell death, cell cycle, angiogenesis, and taxis were also regulated by LTβR signaling. Moreover, we show that activation of the LTβR inhibits the expression of a key adipogenic transcription factor, peroxisome proliferator activated receptor-γ (pparg), suggesting that LTβR signaling may interfere with adipogenic differentiation. Conclusions: Thus, microarray analysis of LTβR-stimulated fibroblasts revealed further insight into the transcriptional response of LTβR signaling and its regulation by the NF-κB family members RelA and RelB. Keywords: cell type comparison (wt vs relA-/- vs relB-/-) after genetic modification using a time course for each cell type (wt, relA-/-, relB-/-) two time points were analysed (0h as control and 10h) using 3 technical replicates resulting in 18 samples in total
2008-12-17 | E-GEOD-11963 | biostudies-arrayexpress
Project description:Rattus norvegicus Relb, RELB proto-oncogene, NF-kB subunit [Source:RGD Symbol;Acc:2321078], is expressed in 6 baseline experiment(s);
| ENSRNOG00000033235 | ExpressionAtlas
Project description:Rattus norvegicus Relb, RELB proto-oncogene, NF-kB subunit [Source:RGD Symbol;Acc:2321078], is differentially expressed in 21 experiment(s);
| ENSRNOG00000033235 | ExpressionAtlas
Project description:Recent studies indicated that the NF-kB RelB subunit may play roles beyond immune modulations. The molecular mechanism that may allow RelB to engage in such diverse physiological activities remains unclear. To better understand the RelB-driven transcriptome, therefore, we subjected wild type and Relb-/- mouse embryonic fibroblast (MEF) to microarray analyses using Illumina MouseRef-8 v2.0 Expression BeadChip. We propose that our transcroptomic analyses will help linking RelB to other important cellular pathways.
2022-05-25 | GSE176446 | GEO
Project description:Background: Lymphotoxin signaling via the lymphotoxin-β receptor (LTβR) has been implicated in several biological processes, ranging from development of secondary lymphoid organs, maintenance of splenic tissue, host defense against pathogens, autoimmunity, and lipid homeostasis. The major transcription factor that is activated by LTβR crosslinking is NF-κB. Two signaling pathways have been described that result in the activation of classical p50-RelA and alternative p52-RelB NF-κB heterodimers. Results: Using microarray analysis, we investigated the transcriptional response downstream of the LTβR in mouse embryoni fibroblasts (MEF) and its regulation by the RelA and RelB subunits of NF-κB. We describe novel LTβR-responsive genes that are regulated by RelA and/or RelB. Interestingly, we found that the majority of LTβR-regulated genes require the presence of both RelA and RelB, suggesting significant crosstalk between the two NF-κB activation pathways. Gene Ontology (GO) analysis confirmed that LTβR-NF-κB target genes are predominantly involved in the regulation of immune responses. However, other biological processes, such as apoptosis/cell death, cell cycle, angiogenesis, and taxis were also regulated by LTβR signaling. Moreover, we show that activation of the LTβR inhibits the expression of a key adipogenic transcription factor, peroxisome proliferator activated receptor-γ (pparg), suggesting that LTβR signaling may interfere with adipogenic differentiation. Conclusions: Thus, microarray analysis of LTβR-stimulated fibroblasts revealed further insight into the transcriptional response of LTβR signaling and its regulation by the NF-κB family members RelA and RelB. Keywords: cell type comparison (wt vs relA-/- vs relB-/-) after genetic modification using a time course
2008-12-18 | GSE11963 | GEO
Project description:Macaca mulatta RELB, RELB proto-onco, NF-kB subunit [Source:VGNC Symbol;Acc:VGNC:76894], is expressed in 3 baseline experiment(s);
| ENSMMUG00000014153 | ExpressionAtlas