Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Blimp-1 and c-Maf regulate Il10 and negatively regulate common and unique proinflammatory gene networks in IL-12 plus IL-27-driven T helper-1 cells [ATAC-Seq]

ABSTRACT: CD4+ Th1 cells producing IFN-g are required to eradicate intracellular pathogens, however if uncontrolled these cells can mediate immunopathology. The cytokine IL-10 is produced by multiple immune cells including Th1 cells during infection and regulates the immune response to minimise collateral host damage. In this study we aimed to elucidate the transcriptional network of genes controlling the expression of Il10 and proinflammatory cytokines, including Ifng in Th1 cells. We show that the transcription factors Blimp-1 and c-Maf each have unique and common effects on cytokine gene regulation and not only co-operate to induce Il10 gene expression in IL-12 plus IL-27 differentiated Th1 cells, but additionally directly negatively regulate key proinflammatory cytokines including Ifng, thus providing mechanisms for reinforcement of regulated Th1 cell responses.

ORGANISM(S): Mus musculus

PROVIDER: GSE197782 | GEO | 2023/08/24

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Blimp-1 and c-Maf regulate Il10 and negatively regulate common and unique proinflammatory gene networks in IL-12 plus IL-27-driven T helper-1 cells [in vitro]

Project description:CD4+ Th1 cells producing IFN-g are required to eradicate intracellular pathogens, however if uncontrolled these cells can mediate immunopathology. The cytokine IL-10 is produced by multiple immune cells including Th1 cells during infection and regulates the immune response to minimise collateral host damage. In this study we aimed to elucidate the transcriptional network of genes controlling the expression of Il10 and proinflammatory cytokines, including Ifng in Th1 cells.

2023-08-24 | GSE197783 | GEO

Tsirvouli2021 - Cytokine and eicosanoid signaling in psoriatic keratinocytes

Project description:The psoKC (psoriatic keratinocyte) model is represnting the behavour of keratinocytes in the later or chronic stage of psoriasis in response to the main cytokines that constitute the characteristic cytokine milieu, namely IFNg and TNFa (mainly derived by Th1 cells), and IL-17 and IL-22 (mainly derived by Th17 cells). Additionally, the model explores the role of exogenous PGE2 through the activation of EP4 receptor signaling. The response to the aforementioned stimuli was not only limited to the cell fate decisions of keratinocytes (proliferation, apoptosis or differentiation) but also include their effect on the psoriatic environment with respect to the secretion of ligands and intercellular-acting stimuli.

2022-12-14 | MODEL2109300001 | BioModels

Identification of a transcription factor network that regulates anti-TNF mediated IL-10 expression in human CD4+ T-cells

Project description:CD4+ T-cells are key players in the pathogenesis of rheumatoid arthritis (RA) through potent production of inflammatory mediators including IL-17A, IFNg and TNF. Anti-TNF therapy has revolutionized the treatment of RA and we previously demonstrated that in vitro treatment of human CD4+ T-cells with the anti-TNF monoclonal antibody adalimumab (ADA) promotes anti-inflammatory IL-10 expression in multiple subpopulations of CD4+ T-cells. Here we investigated the transcriptional mechanisms underlying the IL-10 induction by TNF-blockade in in vitro stimulated CD4+ T-cells. CD4+ T-cells were isolated from PBMC of healthy volunteers by magnetic isolation and cultured for 3 days with anti-CD3/CD28 mAb in the absence or presence of anti-TNF. After culture, CD45RA+ cells were depleted and RNA was extracted for gene expression profiling by RNA-seq and cell nuclei were isolated for chromatin accessibility analysis by ATAC-seq. Gene expression analysis of memory CD4+ T-cells showed a distinct gene signature of 183 genes (q-value <0.05) conferred by anti-TNF treatment. Pathway enrichment analysis of the differentially expressed genes revealed multiple pathways related to cytokine signalling and regulation of cytokine production; in particular, IL10 was the most upregulated gene by anti-TNF, while the proinflammatory cytokines and chemokines IFNG, IL9, IL22 and CXCL10 were significantly downregulated (q-value <0.05). Transcription factor (TF) motif analysis at the differentially open chromatin regions after anti-TNF treatment revealed 58 TF motifs, shared by all donors, enriched at the IL10 locus. We identified 7 TF candidates for the anti-TNF mediated regulation of IL-10, which were either differentially expressed or whose locus was differentially accessible upon anti-TNF stimulation. We postulate that this TF network, which includes MAF and PRMD1, drives transcriptional regulation of IL-10 in anti-TNF treated T-cells.

2024-09-25 | GSE216688 | GEO

IL-10 from intestinal macrophages prevents excessive innate immune responses to bacteria by limiting IL-23 synthesis

Project description:Innate immune responses must be regulated in the intestine to prevent excessive inflammation. Here, using gene reporter mice, we show that a subset of mouse colonic macrophages constitutively produced the anti-inflammatory cytokine IL-10. In mice infected with Citrobacter rodentium, which is considered similar to enteropathogenic Escherichia coli infection in humans, macrophage IL-10 was required to prevent intestinal pathology and to promote survival. The synthesis of the proinflammatory cytokine IL-23 was significantly increased in infected mice with a myeloid cell specific deletion of IL-10 and the addition of IL-10 reduced in vitro IL-23 production by intestinal macrophages. Furthermore, blockade of IL-23 led to reduced morbidity and mortality in the context of macrophage IL-10 deficiency. Transcriptome analysis indicated that the reporter positive and negative colonic macrophage subsets were highly similar, but the reporter positive cells differed for the expression of CD163, an IL-10 target gene, suggesting an autocrine IL-10 signal, and when obtained from infected mice, they had reduced IL-23p19 mRNA. Interestingly, only transfer of the reporter positive cells could rescue IL-10 deficient infected mice. Therefore, these data indicate a pivotal role for a subset of intestinal macrophages that constitutively produces IL-10, perhaps acting in part in autocrine fashion, in controlling excessive innate immune activation, regulation of IL-23 production, and prevention of tissue damage after an acute bacterial infection in the intestine. Two replicates each of IL10+ and IL10- large intestinal macrophages. Data were normalized with the 'rma' function of the Bioconductor package, along with several GEO (GSM616132, GSM616136, GSM616140, GSM868296, GSM868297, GSM868298) and ArrayExpress (E-MEXP-3216: 04-M2WT, 05-M2WT, 06-M2WT) datasets.

2015-05-12 | E-GEOD-58677 | biostudies-arrayexpress

IL-4 induced non-canonical trained immunity in murine BMDMs

Project description:The canonical role IL-4 is to induce M2 macrophage polarization. Herein we report that in addition to its canonical role, IL-4 also induces non-canonical pro-inflammatory response via epigenetic memory. Although IL-4 stimulated macrophages do not produce classic proinflammatory cytokines such as IL-6 and IL-1b, they produce heightened proinflammatory cytokine upon LPS stimulation.

2022-12-31 | GSE184811 | GEO

Transcription profiling of human epidermal keratinocytes treated with IL-1

Project description:Interleukin-1 is a proinflammatory and immunomodulatory cytokine that plays a crucial role in inflammatory diseases of the skin, including bacterial infections, bullous diseases, UV damage and especially psoriasis. To characterize the molecular effects of IL-1 in epidermis, we defined the transcriptional changes in human epidermal keratinocytes 1, 4, 24, and 48 h after treatment with IL-1a. IL-1 significantly regulated 388 genes, including genes associated with proteolysis, adhesion, signal transduction, proliferation, and epidermal differentiation. IL-1 induces many genes that have antimicrobial function. Secreted cytokines, chemokines, growth factors, and their receptors are the prominent targets of IL-1 regulation, including IL-8, IL-19, elafin, C3, and S100A proteins, which implicates IL-1 in the pathogenesis of inflammatory diseases. IL-1 induced not only proliferation-associated genes but also differentiation marker genes such as transglutaminase-1 and involucrin, which suggests that IL-1 plays an important role in the aberrant proliferation and differentiation seen in psoriasis. Correlation of IL-1 regulated genes with the TNFa and IFNg regulated ones showed more similarities between IL-1 and TNFa than IL-1 and IFNg, whereas Oncostatin-M affected a largely unrelated set of genes. IL-1 regulates many genes previously shown to be specifically over-expressed in psoriasis. In summary, IL-1 regulates a characteristic set of genes that define its specific contribution to inflammation and aberrant differentiation in skin diseases. Experiment Overall Design: keratinocytes were treated with 25 ng/ml IL-1 and transcriptomes compared to untreated controls at 1, 4, 24 and 48 h post treatment.

2008-06-16 | E-GEOD-9120 | biostudies-arrayexpress

Inflammation driven by tumor-specific Th1 cells protects against B-cell cancer

Project description:The immune system can both promote and suppress cancer. Chronic inflammation and proinflammatory cytokines such as interleukin (IL)-1 and IL-6 are considered tumor-promoting. In contrast, the exact nature of protective antitumor immunity remains obscure. In this study, we have quantified locally secreted cytokines during primary immune responses against myeloma and B-cell lymphoma in mice. Strikingly, successful cancer immunosurveillance mediated by tumor-specific CD4+ T cells was consistently associated with elevated local levels of both proinflammatory (IL-1aplha, IL-1beta, and IL-6) and T helper 1 (Th1)-associated cytokines (interferon-alpha, IL-2, IL-12). Cancer eradication was achieved by a collaboration between tumor-specific Th1 cells and tumor-infiltrating, antigen-presenting macrophages. Th1 cells induced secretion of IL-1? and IL-6 by macrophages. Th1-derived interferon-? was shown to render macrophages directly cytotoxic to cancer cells, and to induce macrophages to secrete the angiostatic chemokines CXCL9/MIG and CXCL10/IP-10. Thus, inflammation, when driven by tumor-specific Th1 cells, may prevent rather than promote cancer. Tumoricidal macrophages were isolated from Idiotype-specific TCR-transgenic SCID mice injected with MOPC315-containing Matrigel. Control macrophages were obtained from TCR-transgenic SCID mice injected with Matrigel containing antigen-loss MOPC315.

2011-03-15 | E-GEOD-26912 | biostudies-arrayexpress

IL-4 induced non-canonical trained immunity via epigenetic modification

Project description:The canonical role of IL-4 is to induce M2 macrophage polarization. Herein we report that in addition to its canonical role, IL-4 also induces non-canonical pro-inflammatory response via epigenetic memory. Although IL-4 stimulated macrophages do not produce classic proinflammatory cytokines such as IL-6 and IL-1β, they produce heightened proinflammatory cytokine upon LPS stimulation.

2022-12-31 | GSE196099 | GEO

RNAseq of small intestinal organoids from mice treated with the cytokines IFNG, IL-13 and IL-22 for 24 hours

Project description:The intestinal epithelium is our first line of defense against infections of the gut and the plasticity in cellular differentiation of the intestinal epithelium is an important part of this response. The changes in cellular composition is driven by immune cell derived cytokines. Here we use signature cytokines of different type of immune responses applied to small intestinal organoids to model how different immune responses affect intestinal epithelial development. Simplified, IFNG represents type I immunity against intracellular pathogens such as viruses, IL-13 represents type II immunity against infections such as parasites and IL-22 represents type III immunity against extracellular bacterial infections. To not influence organoid formation, organoids were grown 24 hours without cytokines, and then 10 ng/mL of cytokine was applied for 24 hours before harvesting RNA. Furthermore, IFNG is supplied in combination with the other cytokines as cytokines are rarely found alone in an inflammation setting. We find that these cytokines affect developmental pathways of the intestinal epithelium and affect the cellular composition of the intestinal epithelium.

2022-05-08 | E-MTAB-9182 | biostudies-arrayexpress

Unleashing natural IL-18 activity using an anti-IL-18BP blocker antibody induces potent immune stimulation and anti-tumor effects

Project description:Recombinant cytokines have limited anti-cancer efficacy mostly due to narrow therapeutic window and systemic adverse effects. IL-18 is an inflammasome induced proinflammatory cytokine that enhances T and NK cell activity and stimulates IFNg production. The activity of IL-18 is naturally blocked by a high affinity endogenous binding protein (IL-18BP). IL-18BP is induced in the tumor microenvironment (TME) in response to IFNg upregulation in a negative feedback mechanism. In this study we found that IL-18 is upregulated in the TME compared to the periphery across multiple human tumors and most of it is bound to IL-18BP. Bound IL-18 levels were largely above the amount required for T cell activation in vitro, implying that releasing IL-18 in the TME could lead to potent T cell immune activation. To restore the activity of endogenous IL-18 we generated COM503, a high affinity anti-IL-18BP antibody (Ab), that blocks the IL-18BP:IL-18 interaction and displaces pre-complexed IL-18 to enhance T cell and NK cell activation. In vivo, administration of a surrogate anti-IL-18BP Ab, either alone or in combination with anti-PD-L1 Ab, resulted in significant tumor growth inhibition and increased survival across multiple mouse tumor models. Moreover, anti-IL-18BP Ab induced pronounced TME-localized immune modulation including an increase in polyfunctional non-exhausted T and NK cell numbers and activation. In contrast, no increase in inflammatory cytokines and lymphocyte numbers or activation state was observed in serum and spleen. Taken together, blocking IL-18BP using an Ab is a promising novel approach to harness cytokine biology for the treatment of cancer.

2024-03-15 | GSE239473 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data