Similar Datasets
Project description:RNA-seq of mouse colon tissue treated with engineered IL-22 variants
| PRJNA672342 | ENA
Project description:RNA-seq analysis of human CD8+ T cells treated with PBS, WT IL-10, super-10, or 10-DE.
2021-10-28 | GSE160332 | GEO
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: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: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: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:Necrotizing enterocolitis (NEC) is a devastating intestinal inflammatory disorder that primarily affects premature infants. Despite decades of research, this disease remains a significant cause of death in the absence of efficient therapeutics. Interleukin (IL)-22 has been shown to play a critical role in maintaining the gut barrier, promoting epithelial regeneration, and controlling intestinal inflammation in adult animal models with an established microbiome. However, the importance of IL-22 signaling in the regulation of gut homeostasis and protection in neonates that lack an established microbiome remains unknown. Therefore, the aim of the current study is to investigate the role of IL-22 in the neonatal intestinal epithelium under homeostatic and inflammatory conditions by using a mouse model of NEC. Our data reveal that Il22 expression in neonatal murine intestine is negligible until weaning. In addition, both human and murine neonates lack IL-22 production during NEC. Mice deficient in IL-22 or mice lacking the expression of IL-22 receptor in intestinal epithelial cells, display a similar susceptibility of neonates to NEC consistent with the lack of endogenous IL-22 at this critical stage of intestinal development. Conversely, treatment with recombinant IL-22 during NEC substantially reduces disease severity. This IL-22-mediated protection is associated with enhanced epithelial regeneration and increased expression of several antimicrobial genes. Strikingly, despite an IL-22-mediated induction of an antimicrobial transcriptional program, the composition of the intestinal microbial communities remains unchanged. Taken together, this study demonstrates that an IL-22 signaling axis promotes protection against neonatal NEC through the induction of epithelial cell regeneration.
2021-05-18 | GSE155172 | GEO
Project description:Psoriasis is an inflammatory skin disease and the exact pathogenesis has not been fully illuminated yet. It has been demonstrated that interleukin-22 (IL-22) plays a significant role in the pathogenesis of psoriasis. Our study aimed to explore the role of IL-22 and its target miRNAs in pathogenesis of psoriasis.
2015-08-27 | GSE72396 | GEO
Project description:IL-22 plays a critical role in defending against mucosal infections, but how IL-22 production is regulated is incompletely understood. Here, we show that mice lacking IL-33 or its receptor ST2 (IL-1RL1) were more resistant to Streptococcus pneumoniae lung infection than wild-type animals, and that single nucleotide polymorphisms in IL33 and IL1RL1 were associated with pneumococcal pneumonia in humans. The effect of IL-33 on S. pneumoniae infection was mediated by negative regulation of IL-22 production by innate lymphoid cells (ILCs), but independent of ILC2s as well as IL-4 and IL-13 signaling. Moreover, IL-33´s influence on antibacterial defense was dependent on housing conditions of the mice, and mediated by the modulatory effect of IL-33 on the intestinal microbiota. Collectively, we reveal that IL-33 controls IL-22-dependent antibacterial defense by modulating the microbiota. Our study thus provides insight into the bidirectional crosstalk between the innate immune system and the microbiota and how it shapes susceptibility to bacterial infection.
2024-03-19 | GSE236343 | GEO