Gene expression profiles in the ileal and colonic epithelial cells from Interleukin (IL)-23-deficient mice and IL-22-deficient mice
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE236445 | GEO | 2023/09/08
REPOSITORIES: GEO
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Project description:IL-23 producing IL-10Rα-deficient gut macrophages elicit an IL-22-driven pro-inflammatory epithelial cell response
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Project description:Interleukin 23 (IL-23) triggers pathogenic features in pro-inflammatory, IL-17-secreting T cells (Th17 and Tγδ17) that play a key role in the development of inflammatory diseases. However, the IL-23 signaling cascade remains largely undefined. Here we used quantitative phosphoproteomics to characterize IL-23 signaling in primary murine Th17 cells. We quantified 6,888 phosphorylation sites in Th17 cells, and found 168 phosphorylations regulated upom IL-23 stimulation. IL-23 increased the phosphorylation of the myosin regulatory light chain (RLC), an actomyosin contractibility marker, in Th17 and Tγδ cells. IL-23-induced RLC phosphorylation required JAK2 and ROCK catalytic activity, and the study of the IL-23/ROCK axis revealed an unexpected role of IL-23 in the migration of Tγδ17 and Th17 cells. Moreover, pharmacological inhibition of ROCK reduced Tγδ17 recruitment to inflamed skin upon challenge with inflammatory agent Imiquimod. This work: i) provides new insights into phosphorylation networks that control Th17 cells, ii) widely expands the current knowledge on IL-23 signaling, and iii) contributes to the increasing list of immune cells subsets characterized by global phosphoproteomic approaches.
2020-03-25 | PXD016633 | Pride
Project description:Interleukin-23 (IL-23) and IL-17 are cytokines currently being targeted in clinical trials. Although inhibition of these cytokines is effective for treating psoriasis, IL-12/23 inhibition attenuates Crohn's disease, while IL-17A or IL-17RA inhibition exacerbates disease. This dichotomy between IL-23 and IL-17 was effectively modeled in the mdr1a- /- mouse model of colitis. IL-23 inhibition attenuated disease by decreasing colonic inflammation while enhancing Treg accumulation. Exacerbation of colitis by IL-17A or IL-17RA inhibition was associated with severe weakening of the intestinal epithelial barrier, culminating in increased colonic inflammation and accelerated mortality. These data show that IL-17A acts on intestinal epithelium to promote barrier function and provides insight into mechanisms underlying exacerbation of Crohn's disease when IL-17A or IL-17RA is inhibited.
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Project description:IL-23 producing IL-10Rα-deficient gut macrophages elicit an IL-22-driven pro-inflammatory epithelial cell response [dataset 2]
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Project description:IL-23 producing IL-10Rα-deficient gut macrophages elicit an IL-22-driven pro-inflammatory epithelial cell response [dataset 1]
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Project description:Cryopreserved human PBMCs from six donors were stimulated with anti-CD3/CD28 beads in the presence or absence of 100ng/ml IL-23 for 22 hours. RNA samples were assessed for consistency with a Bioanalyzer (Agilent) and quantified by a Nanodrop® ND 1000 Spectrophotometer (Nanodrop Technologies, USA). Expression array data was quantile normalised, detection above background statistical testing performed, comparison between activated un-stimulated versus activated IL-23 stimulated conditions performed as a paired test using the Illumina Custom differential expression algorithm (all implemented in Illumina BeadStudio GeneExpression Module v3.2). Two sample groups were compared, each with 6 biological replicates. Group 1 was stimulated with CD3CD28 antibody coated beads as a control group for 22hours. Group 2 was stimulated as the control group and treated with IL-23 100ng/ml for the same time period. Keywords: Cytokine Treatment
2009-10-10 | GSE10080 | GEO
Project description:We performed RNA-Seq analysis and compared three groups 1) WT+IL-23 v. WT+GFP (control), 2) Mdl1-/-+IL-23 v. WT+GFP (control), and 3) WT+IL-23 v. Mdl1-/-+IL-23. Sets of differentially expressed genes (DEG) were defined on the basis of standard thresholds i.e. a |log2FC|≥2 combined with an adjusted p-value≤0.01 against the control group. Differential expression analysis revealed 1171 (619 up-regulated and 552 down-regulated) DEGs in WT+IL-23 v. WT+GFP, 414 (303 up-regulated and 111 down-regulated) DEGs in Mdl1-/-+IL-23 v. WT+GFP, and 260 (122 up-regulated and 138 down-regulated) DEGs in WT+IL-23 v. Mdl1-/-+IL-23
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Project description:Salmonella enterica serotype Typhimurium cause a localized enteric infection in immunocompetent patients while human immunodeficiency virus (HIV)-infected patients develop a life threatening bacteremia. We used a rhesus macaque ileal loop model to study how simian immunodeficiency virus (SIV) infection triggers defects in mucosal barrier function that enhance S. Typhimurium dissemination. SIV infection resulted in significant depletion of CD4+ T cells in the intestinal mucosa. Gene expression profiling revealed a defective TH17 response (with suppression of IL-17 and IL-22 expression) and impaired homeostasis of the intestinal epithelium in SIV-infected animals during NTS infection. These findings correlated with an impaired ability of lamina propria CD4+ T cells from SIV-infected macaques to produce IL-17 upon ex vivo stimulation, while production of IFNï§ was not affected. This cytokine imbalance in SIV-infected animals was associated with reduced expression of genes required for intestinal epithelial maintenance and repair, increased fluid secretion during NTS infection, epithelial damage and translocation of a non-invasive S. Typhimurium mutant. Although no defects in neutrophil recruitment were noted, the ileum of SIV-infected animals contained lower levels of the enzyme myeloperoxidase, which may indicate defects in neutrophil killing capacity. S. Typhimurium was recovered in markedly increased numbers from the mesenteric lymph nodes of SIV-infected macaques, illustrating the increased potential for systemic dissemination during co-infection. Our data suggest that SIV-infection causes a multi-factorial defect in mucosal barrier function that promotes bacterial dissemination. Keywords: Disease state analysis Comparison of ileal gene expression profiles in SIV infected rhesus macaques in response to Salmonella challange.
2010-05-26 | E-GEOD-10567 | biostudies-arrayexpress
Project description:Macrophages acquire distinct phenotypes during tissue stress and inflammatory responses. Classically, macrophages are categorized into two different subsets named inflammatory M1 and anti-inflammatory M2 macrophages. We herein identified a unique pathogenic macrophage subpopulation, named M17, driven by IL-23 with a distinct gene expression profile including cytokines and membrane molecules. In contrast to M1 and M2-polarized macrophages, M17 macrophages express high levels of CXCR5 on the cell surface and produce large amounts of IL-17A, IL-22 and IFN-γ. IL-23 induces IL-17A expression in macrophages through the signal transducer and activator of transcription 3 (STAT3)-retinoid related orphan receptor-γ T (RORγT) pathway, while induces IFN-γ through T-bet. Importantly, IL-23-induced M17 macrophage polarization promotes the pathogenesis of psoriasis in vivo. The characteristics and significances of M17 macrophage subpopulation in the physiological status and pathogenesis caused by infections, tumors and graft rejection needs to be explored.
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