Profiling of IL-33 target genes incytotoxic T cells, T helper 1 and T helper 2 cells
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE204694 | GEO | 2023/10/17
REPOSITORIES: GEO
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Project description:The pleiotropic alarmin interleukin-33 (IL-33) promotes the activity of many innate and adaptive immune cell subsets. Its receptor ST2 is constitutively expressed at high levels by type 2-biased immune cells including CD4+ T helper 2 (Th2) cells, innate lymphoid cells type 2 and highly potent regulatory T cells, allowing rapid sensing of IL-33 alarmin signals (Peine et al., 2015). In contrast, during viral infections, antiviral CD8+ cytotoxic T cells (CTLs) and CD4+ Th1 cells express ST2 at a low level in a transient and activation dependent way, suggesting that the ST2-coding gene Il1rl1 is regulated in a cell-type specific manner (Bonilla et al., 2012). To better understand the transcriptional regulation of the Il1rl1 gene in distinctly polarized T cells, we here performed RNA-Sequencing of in vitro activated, ST2 expressing CTLs, Th1 and Th2 cells. Further, to decipher the T cell subset-specific consequences of IL-33 sensing, we profiled early changes in transcriptional activity of CTLs, Th1 cells and Th2 cells upon stimulation with IL-33. Lastly, to better understand the role of IL-33 during an acute infection with lymphocytic choriomeningitis virus (LCMV), activated CD44+ CTLs were flowcytometrically sorted from infected C57BL/6 wildtype and Il1rl1 gene-targeted mice (Il1rl1-ExAB-/-) and subjected to combined single-cell gene expression and single cell TCR-Seq analysis. This SuperSeries is composed of the SubSeries listed below.
2023-10-17 | GSE204695 | GEO
Project description:The pleiotropic alarmin interleukin-33 (IL-33) promotes the activity of many innate and adaptive immune cell subsets. Its receptor ST2 is constitutively expressed at high levels by type 2-biased immune cells including CD4+ T helper 2 (Th2) cells, innate lymphoid cells type 2 and highly potent regulatory T cells, allowing rapid sensing of IL-33 alarmin signals (Peine et al., 2015). In contrast, during viral infections, antiviral CD8+ cytotoxic T cells (CTLs) and CD4+ Th1 cells express ST2 at a low level in a transient and activation dependent way, suggesting that the ST2-coding gene Il1rl1 is regulated in a cell-type specific manner (Bonilla et al., 2012). To better understand the transcriptional regulation of the Il1rl1 gene in distinctly polarized T cells, we here performed RNA-Sequencing of in vitro activated, ST2 expressing CTLs, Th1 and Th2 cells.
2023-10-17 | GSE204692 | GEO
Project description:Memory CD4+ T helper (Th) cells are crucial for acquired immunity and protection from infectious microorganisms, and also drive pathogenesis of chronic inflammatory diseases, such as asthma. ST2hi memory-type Th2 cells have been identified as a pathogenic subpopulation capable of directly inducing eosinophilic airway inflammation. These ST2hi pathogenic Th2 cells produce large amounts of IL-5 upon stimulation via their TCR, but not in response to IL-33. In contrast, IL-33 alone induces cytokine production in ST2+ group 2 innate lymphoid cells (ILC2). We investigated the molecular mechanism that controls the innate function of IL-33-induced cytokine production, and identified a MAPK phosphatase Dusp10, as a key negative regulator of IL-33–induced cytokine production in Th2 cells. We found that Dusp10 is expressed by ST2hi pathogenic Th2 cells but not by ILC2, and Dusp10 expression inhibits IL-33-induced cytokine production by preventing GATA3 activity through inhibition of p38 MAPK phosphorylation. Strikingly, deletion of Dusp10 rendered ST2hi Th2 cells able to directly respond to IL-33 exposure and produce IL-5. Thus, DUSP10 constrains IL-33–induced cytokine production in ST2hi pathogenic Th2 cells by controlling p38-mediated GATA3 function.
2018-09-23 | GSE116842 | GEO
Project description:Cryptococcal disease pathogenesis is associated with the induction of type 2 immune response which is largely mediated by adaptive T helper cells. Recently, epithelial cell-derived IL-33 and IL-25 are recognized as key mediators in driving pathogenic type 2 inflammation during C. neoformans infection. Although IL-25 and IL-33 exhibit a combinatorial and closely related function, the differential effect of these cytokines in the regulation of host immune response against C. neoformans infection is still elusive. We observed a predominantly increase of IL-25/IL-33 responsive Th cells within the lung after infection, especially at the chronic infection phase. The ex vivo stimulation of cryptococcal-specific Th cells demonstrated combinatorial effect of IL-25 and IL-33 in promoting the production of type 2 cytokines. A comparative transcriptomic analysis revealed coordinatel effects of these cytokines in promoting activation, survival, and homeostasis of adaptive Th cells during C. neoformans infection. The expression of type 2 cytokines and chemokine was absent in Th cells of Il17rb-/- mice, indicating the requirement of IL-25-mediated Th2-type immune responses during C. neoformans infection. Further analysis of the degree of virulence indicated a positive correlation between the frequency of IL-17RB/ST2-expressing Th cells and cryptococcal brain dissemination in vivo.
2023-06-18 | GSE229703 | GEO
Project description:ST2 heterodimerizes with IL-1RAcp to form the receptor for IL-33, which is primarily associated with allergic inflammation by inducing Th2 responses. Recently, however, IL-33 was found to be expressed in the central nervous system and in retinal Muller cells which imply functions, as yet undescribed, beyond Th2 mediated inflammation. Muller cells support the health of the retina and photoreceptors and are also involved in inflammation in retinal degeneration. It is not known how IL-33/ST2 functions in this capacity. We recently found that ST2 ko mice are protected from CLE-induced photoreceptor loss, implying a detrimental effect of IL33/ST2 in CLE. We wish to perform microarray analysis using WT and ST2 KO mice in CLE model to better understand the mechanism by which IL-33/ST2 regulates retinal degeneration.
2015-12-17 | GSE74695 | GEO
Project description:Interleukin-33 (IL-33) is a novel member of the IL-1 family of cytokines that plays diverse roles in the regulation of immune responses. IL-33 exerts its effects by binding to a heterodimeric receptor complex consisting of interleukin-1 receptor like 1 (IL1RL1) and an accessory receptor protein IL-1RAcP resulting in the production and release of proinflammatory cytokines. A detailed understanding of the signaling pathways activated by IL-33 remains elusive. To elucidate IL-33 mediated signaling, we performed a global quantitative phosphoproteomic analysis using stable isotope labeling by amino acids in cell culture. Employing anti-phosphotyrosine antibodies and titanium dioxide-based enrichment strategies, we identified 6,207 phosphorylation sites mapping to 2,013 phosphoproteins of which more than 185 phosphosites are regulated by IL-33 stimulation. Our findings will greatly expand the understanding of IL-33 signaling and provide novel therapeutic targets for IL-33/IL-33R-associated diseases in humans.
2015-01-29 | PXD000984 | Pride
Project description:ST2 heterodimerizes with IL-1RAcp to form the receptor for IL-33, which is primarily associated with allergic inflammation by inducing Th2 responses. Recently, however, IL-33 was found to be expressed in the central nervous system and in retinal Muller cells which imply functions, as yet undescribed, beyond Th2 mediated inflammation. Muller cells support the health of the retina and photoreceptors and are also involved in inflammation in retinal degeneration. It is not known how IL-33/ST2 functions in this capacity. We recently found that ST2 ko mice are protected from CLE-induced photoreceptor loss, implying a detrimental effect of IL33/ST2 in CLE. We wish to perform microarray analysis using WT and ST2 KO mice in CLE model to better understand the mechanism by which IL-33/ST2 regulates retinal degeneration. CLE (Constant Light Exposure) is a model of retinal damage/degeneration in mice. Mice are exposed to bright light 24 hours a day for a period of time which damages retina photoreceptors. This damage is assessed by histology, optical coherence tomography (OCT), which measures retina thickness in vivo. In this experiment, the WT and ST2 KO mice (5 mice per genotype per time point) will be exposed to 1200-lux constant light for 0, 3, 10 days. The retinal RNA will be isolated and analyzed for differential gene expression by microarray.
2015-12-17 | E-GEOD-74695 | biostudies-arrayexpress
Project description:IL-33 is a nuclear cytokine from the IL-1 family that plays important roles in health and disease. Under healthy conditions, IL-33 is constitutively expressed to high levels in the nucleus of producing cells in various human and mouse tissues. The extracellular function of IL-33 cytokine has been well documented, but it remains unclear whether intracellular nuclear IL-33 has additional functions in the nucleus. Here, we used a global proteomic approach based on quantification of 5000 individual proteins by high-resolution mass spectrometry to compare the extracellular and intracellular roles of IL-33 in primary human endothelial cells, a major source of IL-33 protein in human tissues. Large-scale analysis of protein expression was performed either after stimulation of the cells with the IL-33 mature form IL-3395-270 (during 6h or 24h) or after siRNA knockdown of intracellular IL-33 (two experiments, each with a different pool of distinct siRNAs, noted siRNA1 and siRNA2). In each case, proteins were fractionated by 1D SDS-PAGE in 12 gel bands, and label-free quantitative analysis was performed. The present dataset contains the files for the two experiments of knockdown of endogenous nuclear IL-33 expression: - RNA silencing strategy 1. Knockdown of endogenous nuclear IL-33 expression was performed with a pool of four distinct siRNAs (Dharmacon ON-TARGETplus SMARTpool IL-33 siRNAs) that have been specifically modified for efficient silencing of the target gene with reduced off-target effects. Cells transfected with these siRNA duplexes (si1) were compared with those transfected with the provided controls (CTsi1). Three independent biological replicates (noted _A, _B, _C) were prepared and analyzed for each condition, leading to 6 different samples. Each of them was fractionated into 12 gel bands analyzed by nanoLC-MS/MS, leading to 72 raw files. - RNA silencing strategy 2. The second knockdown strategy was based on the use of an independent pool of three siRNAs targeting IL-33, predesigned by another provider using new and critical siRNA design rules (Sigma MISSION Predesigned Il-33 siRNAs based on Rosetta siRNA design algorithm). Cells transfected with these siRNA duplexes (si2) were compared with those transfected with the provided controls (CTsi2). Three independent biological replicates (noted _A, _B, _C) were prepared and analyzed for each condition, leading to 6 different samples. Each of them was fractionated into 12 gel bands analyzed by nanoLC-MS/MS, leading to 72 raw files.
2016-10-12 | PXD004141 | Pride
Project description:Determination of the molecular mechanism of IL33 on glioma cells Since IL-33 is known to associate with chromatin and regulate transcriptional activity and that nuclear expression of IL-33 increases glioma progression, we determined Nuclear IL-33 regulates the expression and secretion of inflammatory cytokines in glioma cells. Using these parameters 340 genes were induced by the ectopic expression of IL-33 and an additional 377 genes were downregulated. Gene ontology terms over-represented in the genes induced by IL-33 include three major clusters that associate with cytokine activity and inflammation
2020-08-21 | GSE153486 | GEO
Project description:Interleukin-33 (IL-33), a member of the IL-1 superfamily cytokines, is an endogenous danger signal and a nuclear-associated cytokine. It is one of the essential mediators of both innate and adaptive immune responses. Aberrant IL-33 signaling has been demonstrated to play a defensive role against various infectious and inflammatory diseases. Although the signaling responses mediated by IL-33 have been previously reported, the temporal signalingdynamicsare yet to be explored. Towards this end,we applied quantitative temporal phosphoproteomics analysis to elucidate pathways and proteins induced by IL-33 in THP1 monocytes. Employing TMT labeling-based quantitation and titanium dioxide (TiO2)-based phosphopeptide enrichment strategy followed by mass spectrometry analysis, we identified 14,515 phosphorylation sites mapping to 4,174 proteins across (0 min to 240 mins)time points.
2022-02-16 | PXD028673 | Pride