Epithelial-derived IL-23 promotes oral mucosal immunopathology
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1016477 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR26057503.fastq.gz | Fastqsanger.gz | |||
| SRR26057504.fastq.gz | Fastqsanger.gz | |||
| SRR26057505.fastq.gz | Fastqsanger.gz | |||
| SRR26057506.fastq.gz | Fastqsanger.gz | |||
| SRR26057507.fastq.gz | Fastqsanger.gz |
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Project description:At mucosal surfaces, epithelial cells provide a structural barrier and an immune defense system. However, dysregulated epithelial responses can contribute to disease states. Here, we demonstrate that epithelial intrinsic production of IL-23 triggers an inflammatory loop in the prevalent oral disease, periodontitis. Epithelial IL-23 expression localized to areas proximal to the disease-associated microbiome, is evident both in experimental models and in patients with common and genetic forms of disease. Mechanistically, flagellated microbial species of the periodontitis microbiome, trigger epithelial IL-23 induction in a TLR5-dependent manner. Intriguingly, unlike other Th17-driven diseases, here non-hematopoietic cell-derived IL-23 serves as an initiator of pathogenic inflammation. Beyond periodontitis, analysis of publicly available datasets reveals expression of epithelial IL-23 in settings of infection, malignancy, and autoimmunity, suggesting a broader role for epithelial-intrinsic IL-23 in human disease. Collectively, this work highlights an unappreciated role for the barrier epithelium in the induction of IL-23-mediated inflammation.
2024-05-08 | GSE243173 | GEO
Project description:Animal model implicates microbiota-triggered oral mucosal Th17 cells as drivers of local immunopathology and therapeutic targets in periodontitis.
2018-12-31 | GSE118166 | GEO
Project description:Background & Aims: The IL-23/IL-17 axis plays an important role in the pathogenesis of autoimmune diseases and the pathological consequences of infection. We previously showed that immunopathologic mechanisms mediated by inflammatory monocytes underlie the severe focal liver damage induced by the protozoan parasite, Entamoeba histolytica. Here, we analyze the contribution of the IL-23/IL-17 axis to the induction and subsequent recovery from parasite-induced liver damage. Methods: IL-23p19-/-, IL-17A/F-/-, CCR2-/-, and WT mice were intra-hepatically infected with E. histolytica trophozoites and disease onset and recovery were analyzed by magnetic resonance imaging. The expression of liver-specific genes and proteins during infection was examined by qPCR, microarray, FACS analysis and immunohistochemistry. Immuno-depletion and substitution experiments were performed in IL-23p19-/- and WT mice to investigate the role of IL-13 in disease outcome. Results: Liver damage in infected IL-23p19-/-, IL-17A/F-/-, CCR2-/- mice was strongly attenuated compared with that in WT mice. IL-23p19-/- mice showed reduced expression of IL-17 and CCL2 genes and proteins. Increased numbers of IL-13-producing CD11b+Ly6Clo regenerative monocytes were associated with disease attenuation in IL-23p19-/- mice. Immuno-depletion of IL-13 in IL-23-/- mice reversed this attenuation and treatment of infected WT mice with an IL-13/anti-IL-13-mAb complex supported liver recovery. Conclusions: The IL-23/IL-17 axis plays a critical role in the immunopathology of hepatic amebiasis. IL- 13 secreted by CD11b+Ly6Clo monocytes supports recovery from liver damage. An IL-13/anti-IL13- mAb complex mimics this function, suggesting a novel therapeutic option to support tissue healing after liver damage.
2016-10-03 | GSE73686 | GEO
Project description:Innate lymphoid cells (ILCs) are crucial for the immune surveillance at mucosal sites. ILCs coordinate early eradication of pathogens and contribute to tissue healing and remodelling, features that are dysfunctional in patients with cystic fibrosis (CF). The mechanisms by which ILCs contribute to CF-immunopathology are ill-defined. Here, we report that group 2 ILCs (ILC2s) transdifferentiated into IL-17-secreting cells in the presence of the epithelial derived-cytokines IL-1β, IL-23 and TGF-β. This conversion was abrogated by IL-4 or vitamin D3. IL-17 producing ILC2s induced IL-8 secretion by epithelial cells and their presence in nasal polyps of CF patients is associated with neutrophilia. Our data suggest that ILC2s undergo transdifferentiation in CF nasal polyps in response to local cytokines, which are induced by infectious agents.
2019-03-26 | GSE124926 | GEO
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:Dysbiotic microbiome triggers Th17 cells to mediate oral mucosal immunopathology in mice and humans
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Project description:Wound healing within the oral mucosa results in minimal scar formation compared to wounds within the skin. We have recently demonstrated distinct differences in the ageing profiles of cells (oral mucosal and patient-matched skin fibroblasts) isolated from these tissues. We hypothesize that the increased replicative potential of oral mucosal fibroblasts may confer upon them preferential wound healing capacities. Passage-matched early cultures of oral mucosal fibroblasts and skin fibroblasts demonstrated distinct gene expression profiles with a number of genes linked to wound healing/tissue repair. We analyzed the gene expression profiles of oral mucosal and patient-matched skin fibroblasts for multiple patients both prior to (0h) and (6h) following a wounding stimulus. Differences in the gene expression profiles of oral mucosal and patient-matched skin fibroblasts were anlazyed for multiple patients both prior to (0h) and (6h) following a wounding stimulus. Serum starvation and subsequent stimulation provides a model for wounding and RNA extracted at 0h and 6h following this stimulus was hybridized to Affymetrix microarrays for analysis. We sought to compare the expression profiles both between oral and normal fibroblasts, in both serum depleted and stimulated conditions and also compare differences between patients.
2011-01-01 | E-GEOD-21648 | biostudies-arrayexpress
Project description:Wound healing within the oral mucosa results in minimal scar formation compared to wounds within the skin. We have recently demonstrated distinct differences in the ageing profiles of cells (oral mucosal and patient-matched skin fibroblasts) isolated from these tissues. We hypothesize that the increased replicative potential of oral mucosal fibroblasts may confer upon them preferential wound healing capacities. Passage-matched early cultures of oral mucosal fibroblasts and skin fibroblasts demonstrated distinct gene expression profiles with a number of genes linked to wound healing/tissue repair. We analyzed the gene expression profiles of oral mucosal and patient-matched skin fibroblasts for multiple patients both prior to (0h) and (6h) following a wounding stimulus.
2011-01-01 | GSE21648 | GEO
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.
2015-08-20 | GSE72212 | 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
2022-07-02 | GSE133830 | GEO