Tifa-/- vs Tifa+/+ small intestinal organoids stimulated with water, IL-22, IL-22+ADP-Heptose
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Illumina NovaSeq 6000
ORGANISM(S): Mus musculus
SUBMITTER:
PROVIDER: E-MTAB-14831 | biostudies-arrayexpress |
SECONDARY ACCESSION(S): ERP169216
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Tifa-/- vs Tifa+/+ small intestinal organoids stimulated with water, IL-22, IL-22+ADP-Heptose
| PRJEB85839 | ENA
Project description:Bulk RNA sequencing of ileal tissue from germline Tifa-/- mice versus wild-type littermate control mice
2025-05-01 | E-MTAB-14833 | biostudies-arrayexpress
Project description:Host immunity limits iron availability to pathogenic bacteria, but whether immunity limits pathogenic bacteria from accessing host heme, the major source of iron in the body, remains unclear. Using Citrobacter rodentium, a mouse enteric pathogen and Escherichia coli, a major cause of sepsis in humans as models, we find that interleukin-22, a cytokine best known for its ability to promote epithelial barrier function, also suppresses the systemic growth of bacteria by limiting iron availability to the pathogen. Using an unbiased proteomic approach to understand the mechanistic basis of IL-22 dependent iron retention in the host, we have identified that IL-22 induces the production of the plasma hemoglobin scavenger haptoglobin and heme scavenger hemopexin. Moreover, the anti-microbial effect of IL-22 depends on the induction of hemopexin expression, while haptogloblin is dispensable. Impaired pathogen clearance in infected Il22-/- mice was restored by hemopexin administration and hemopexin-deficient mice had increased pathogen loads after infection. These studies reveal a previously unrecognized host defense mechanism regulated by IL-22 that relies on the induction of hemopexin to limit heme availability to bacteria leading to suppression of bacterial growth during systemic infections.
2017-02-03 | PXD005666 | Pride
Project description:Infection by attaching and effacing (A/E) pathogens poses a serious threat to public health, as was highlighted by the recent outbreak of E. coli O157:H7 infection in the United States. Here, by using a murine A/E pathogen, Citrobacter rodentium, we demonstrate that C. rodentium infection is lethal to IL-22-/- mice within two weeks. IL-22, in the early phase of infection, is indispensable for preventing the invasion of bacteria through the intestinal epithelium, and thereby preventing systemic spread and mortality. We also show that IL-23 is required for the early induction of IL-22 during C. rodentium infection. Finally, our data suggest that IL-22 exerts its function by boosting the innate immune responses of colonic epithelial cells, especially though the induction of anti-microbial proteins, RegIIIβ and RegIIIγ. Experiment Overall Design: Control or IL-22-treated mouse colon in triplicate.
2008-04-07 | E-GEOD-10010 | biostudies-arrayexpress
Project description:The cytokine IL-22 promotes tumor progression in murine models of colorectal cancer (CRC). However, the clinical significance of IL-22 in human CRC remained unclear. Using a rigorous discovery/verification analysis of tumor gene expression from over 1,000 patients, we discovered that among CRC patients with high expression of either or both subunits of the heterodimeric IL-22 receptor, KRAS mutation confers poor prognosis. Analysis of human CRC cell lines and primary tumor organoids, including a DLD-1 isogenic cell line pair that differed only in KRAS mutation status, showed that IL-22 and mutant KRAS cooperatively enhance cancer cell proliferation. The purpose of this study was to identify unique mechanisms of interaction between IL-22 signaling and mutant KRAS. Taking advantage of the DLD-1 isogenic pair with match IL-22 receptor expression, differing only in the presence or absence of mutant KRAS global transcriptomic changes were explored in an unbiased manner following IL-22 stimulation. RNA-sequencing was performed on DLD-1 isogenic cells stimulated with 10ng/mL IL-22 for 2h to identify early transcriptional changes and after 24h to explore late changes. Given that IL-6 receptor expression does not interact with mutant KRAS in a prognostically significant manner, nor did it enhance proliferation in KRAS mutant versus WT cells, DLD-1 isogenic cells were also stimulated with 10ng/mL IL-6 for 2 and 24h to identify pathways uniquely regulated by IL-22 and not IL-6.
2020-04-24 | GSE149262 | GEO
Project description:The Experiment was performed to understand the changes in expression profile of enteric glia cells in vitro to specific cytokines. Enteric glia are crucial regulators of gastrointestinal motility and immunity; however, it is not fully understood what specific cytokines can elicit a response in enteric glia. Acute T-cell activation rapidly impacts enteric glia activation, and induces cell death pathways, which negatively impacts small intestinal transit. Therefore, this experiment has been crucial to identify the specific responses of enteric glia to recombinant murine IFNγ, TNFα, Il-13, Il-17A and Il-1b. In order to sequence pure enteric glia, a mouse strain of Bl6 mice with a Plp1CreERT insert for glial specificity crossed with mice with a flox controlled tdTomato fluorescent protein on the ROSA26 Locus. From these mice the longitudinal muscle layer with the myenteric plexus stripped off and enzymaticly dissociated. The enteric glia were kept as a primary cell culture and the expression of tdTomato induced with 500 nM (Z)-4-Hydroxytamoxifen (MilliporeSigma). After expansion the glia were FACS sorted and stimulated with the respective cytokine. Finally, the RNA was isolated after 24 hours and sequenced.
2025-07-01 | E-MTAB-14879 | biostudies-arrayexpress
Project description:IBD is a complex autoimmune disease characterized by dysregulated interactions between host immune responses and microbiome at the intestinal epithelium interface. Here we identified shared protein alterations in intestinal epithelial differentiation and function between IBD and Citrobacter rodentium infected FVB mice. We discovered that prophylactic treatment with the mucosal healing therapy IL-22.Fc in the infected FVB mice reduced disease severity and rescued the mice from lethality. Notably, we observed an emergence of intermediate undifferentiated intestinal epithelial cells upon infection, with disrupted expression of the solute transporter machinery as well as components critical for intestinal barrier integrity. Multi-omics analyses revealed that with IL-22.Fc treatment several disease associated changes were prevented (including disruption of the solute transporter machinery), and proper physiological homeostatic functions of the intestine was restored. Taken together, we unveiled the disease relevance of the C. rodentium induced colitis model to IBD and demonstrated the protective role of the mucosal healing therapy IL-22.Fc in ameliorating the epithelial dysfunction.
2023-10-05 | PXD024688 | Pride
Project description:Interleukin (IL) - 22 is a cytokine that plays a critical role in the maintenance of intestinal epithelial homeostasis. Its downstream functions are mediated through ligation of its heterodimeric receptor comprised of IL-22 receptor subunit alpha 1 (IL-22Ra1) and IL-10R2, and subsequent activation of signal transducer and activator of transcription 3 (STAT3). IL-22 signaling can induce genes necessary for intestinal epithelial cell proliferation, tissue regeneration, tight junction fortification, and production of antimicrobials. Emerging studies have also implicated IL-22 signaling in the regulation of intestinal epithelial fucosylation in mice. However, whether IL-22 regulates intestinal fucosylation in human intestinal epithelial cells and the molecular mechanisms that govern this process are unknown. Here, we show that IL-22 signaling regulates expression of the B3GNT7 transcript, which encodes a β1-3-N-acetylglucosaminyltransferase that can participate in the synthesis of poly-N-acetyllactosamine (LacNAc) chains. Additionally, we show that IL-22 signaling regulates levels of the a1-3-fucosylated Lewis X (Lex) blood group antigen and this glycan epitope is primarily displayed on heavily O-glycosylated intestinal epithelial glycoproteins. The IL-22-mediated increase in Lex antigen levels requires B3GNT7, as disruption of B3GNT7 expression moderated the IL-22-dependent increase in Lex antigen levels. Moreover, we show that increased expression of B3GNT7 alone is sufficient to promote increased display of Lex-decorated carbohydrate glycan structures primarily on O-glycosylated intestinal epithelial glycoproteins. Together, the data presented here identify B3GNT7 as a critical intermediary in IL-22-dependent induction of intestinal fucosylation of O-linked glycans and uncover a novel role for B3GNT7 in intestinal glycosylation.
2021-11-27 | GSE154889 | GEO
Project description:Diabetic foot ulcers (DFU) are one of the major complications in type II diabetes patients and can result in amputation and morbidity. Although multiple approaches are used clinically to help wound closure, many patients still lack adequate treatment. Here we show that IL-20 subfamily cytokines are upregulated during normal wound healing. While there is a redundant role for each individual cytokine in this subfamily in wound healing, mice deficient in IL-22R, the common receptor chain for IL-20, IL-22, and IL-24, display a significant delay in wound healing. Furthermore, IL-20, IL-22 and IL-24 are all able to promote wound healing in type II diabetic db/db mice. When compared to other growth factors such as VEGF and PDGF that accelerate wound healing in this model, IL-22 uniquely induced genes involved in reepithelialization, tissue remodeling and innate host defense mechanisms from wounded skin. Interestingly, IL-22 treatment showed superior efficacy compared to PDGF or VEGF in an infectious diabetic wound model. Taken together, our data suggest that IL-20 subfamily cytokines, particularly IL-20, IL-22, and IL-24, might provide therapeutic benefit for patients with DFU.
2017-03-08 | GSE80419 | GEO
Project description:Atopic dermatitis (AD) is a chronic type-2 inflammatory skin disease characterized by epithelial barrier dysfunction. IL-4, IL-13, and IL-22 represent major cytokines contributing to AD-pathogenesis. Models using reconstructed keratinocytes have been used in previous studies, however, did not represent the real skin situation. Here, we report the distinct effects of IL-4, IL-13, and IL-22 on bio-stabilized human skins with intact barriers and resident immune cells. Spatial transcriptomics on AD-lesions and non-lesional skin of patients, and RNA-sequencing, and proteomics were performed in IL-4-, IL-13- and IL-22-treated native skins. Skin barrier integrity was evaluated using electrical impedance spectroscopy. Spatial transcriptomics demonstrated that CLDN1, FLG, and FLG2 were significantly downregulated in the epidermis of AD lesions. IL-4, IL-13, and IL-22 disrupted the skin barrier in the ex vivo human skin by downregulation of the genes and proteins critical for barrier function and keratinization. IL-4 and IL-13 suppressed, whereas IL-22 upregulated the antimicrobial peptides. Interestingly, IL-4 and IL-13 showed a cross-regulation with IL-22, by downregulation of IL-22Rα1 with IL-4 and IL-13 and upregulation of IL-4Rα with IL-22. Three months of dupilumab treatment in AD patients restored the IL-4 and IL-13-dysregulated genes, whereas genes co-regulated or only regulated by IL-22 remained unaltered. In conclusion, this study comprehensively provides insights into the distinct immune profiles following IL-4, IL-13, and IL-22 stimulation in human skin, highlighting their complex interplay in the pathogenesis of AD modulating keratinocyte and immune responses.
2025-12-05 | GSE292848 | GEO