Control of RelB during dendritic cell activation integrates canonical and non-canonical NFkB pathways
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE34990 | GEO | 2012/10/01
SECONDARY ACCESSION(S): PRJNA151093
REPOSITORIES: GEO
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Project description:Dendritic cells (DC) play central roles in coordinating appropriate immune responses to pathogens. In the present study, the genes regulated by NFkB activators, RelB and cRel, in PAMP-induced bone marrow dendritic cells (BMDCs) activation was examined. Total RNA extracted from WT, relb-/-, crel-/-relb-/- bone marrow derived dendritic cells (BMDCs) were subjected to stimulation with CpG or Pam3CSK4.
2012-10-01 | E-GEOD-34990 | biostudies-arrayexpress
Project description:NFkB is a family of transcriptional factors that are responsible for inflammatory and immune gene expression. RelA, RelB and cRel are the transactivation domain containing family members. P50 encoded by Nfkb1 is the primary dimerization partner. Many NFkB deficient mice are embryonic lethal. In order to identify NFkB dependent genes, MEF were isolated from Rela-/-cRel-/-, Rela-/-cRel-/-Nfkb1-/- and Rela-/-Relb-/-cRel-/- embryos at E12.5. They were treated with 100ng/ml LPS for 1hr and then profiled gene expression by microarray.
2016-06-27 | E-MTAB-4412 | 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. 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: Not available
| S-EPMC3634611 | biostudies-literature
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:To investigate the Gene dysregulation caused by loss of RelB and identify candidate genes driving the loss of RelB autoimmune phenotype
2023-02-06 | GSE224515 | GEO
Project description:Gene expression profile of dendritic cells (DC) of mesenteric lymph node (mLN) and lamina propria of small intestine (SI-LP) of control mice and mice lacking RelB expression in DCs at steady state, four days and 14 days after infection with Heligmosomoides polygyrus bakeri (Hpb) Dendritic cells (DCs) are crucial for initiating protective immune responses and have also been implicated in the generation and regulation of Foxp3+ regulatory T cells (Tregs). Specific DC subsets or DC-intrinsic pathways regulate immunity against pathogens but also tolerance to harmless antigens derived from food or microbiota at barrier sites, but underlying mechanisms in the intestinal tract remain poorly defined. Here, we provide evidence that the alternative NF-B family member RelB controls a defined transcriptional program in migratory DC subsets of mesenteric lymph nodes and the small intestinal lamina propria. Functionally, ablation of RelB in dendritic cells result in increased Foxp3+ Treg cell numbers but decreased RORt peripheral Treg cell numbers maintained even under inflammatory conditions. Single-cell RNA-sequencing revealed a complete RelB dependency for the differentiation of cryptopatches and isolated lymphoid follicles-associated DCs (CIA-DCs) in the lamina propria of the small intestine. In addition, we show a RelB-dependent signature of migratory DCs in mesenteric lymph nodes favoring DC-Treg cell interaction by affecting the expression of chemokines (Ccl22, Ccl17), migration behavior (Cd63), co-stimulatory molecule (Cd80, Cd40, Cd200, Tnfsf4), and tolerance-related integrin (Itgb5, Itgb8) expression. Functionally, increased Treg cell numbers in DC-specific RelB knockout animals did not show any risk of increased reactions in a model of food allergy but instead prevented protective Th2 immune responses in the intestines after infection with Heligmosomoides polygyrus bakeri despite their slight steady-state type 2 immune bias. This protection was dependent on elevated Treg cell frequencies during primary infection as a result of bystander immune tolerance. Thus, RelB expression in conventional DCs acts as a rheostat to establish a tolerogenic set point that is maintained even during infection and strong type 2 immune conditions and thereby is a key regulator of intestinal homeostasis.
2023-09-22 | GSE243483 | GEO
Project description:We report here the effect of RelB ablation in CD11c+ cells on the Treg compartment accross various organs.This mice have been backcrossed to a Foxp3 reporter mouse line to enable cell sorting of Tregs with a high purity. Interestingly, RelB ablation in DCs leads to a substantial accumulation of Tregs and these Tregs show a 'tissue Treg' signature including high expression levels of KLRG1, I1LRL1 and Gata3 when compared to Tregs of littermate control mice.
2019-09-11 | GSE134779 | 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