Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Kessler2025 - IL-6 and IL-22 pathway in human hepatocytes

ABSTRACT: IL-6 and IL-22 pathway in human hepatocytes

SUBMITTER: Marcus Kessler

PROVIDER: MODEL2509100001 | BioModels | 2025-11-14

REPOSITORIES: BioModels

ACCESS DATA

Json Xml

Publications

Computational analysis of IL-6/IL-22 signaling in liver disease.

Keßler Marcus D MD Klemt Lara L Kirchner Marius M Ackermann Jörg J Mühl Heiko H Welsch Christoph C Koch Ina I

Bio Systems 20250811

The cytokines interleukin 6 (IL-6) and interleukin 22 (IL-22) are involved in multiple signaling pathways in a variety of cells, e.g. the activation of the acute-phase response, cell homeostasis and tissue repair. However, high concentrations of IL-6 and IL-22 are associated with worse outcomes for patients with liver pathologies such as cirrhosis and chronic liver failure. Consequently, these pathways are tightly controlled by regulatory proteins. Despite their importance to liver function, the ...[more]

PMID: 40803488

Similar Datasets

Distinct Roles of IL-4, IL-13, and IL-22 in Human Skin Barrier Dysfunction and Atopic Dermatitis

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

Arid5a directs autoimmune inflammation through an IL-17 signaling pathway [human]

Project description:Arid5a directs autoimmune inflammation through an IL-17 signaling pathway [human]

| PRJNA1123383 | ENA

Gene expression profile of human epidermal keratinocytes in response to IFNgamma, IL-4, IL-6, IL-17A and IL-22

Project description:To understand the role of epidermal keratinocytes in immunopathology of skin diseases with predominant T helper (Th) cell responses, we measured the genome-wide transcriptional profile of human keratinocytes in response to IFNgamma, IL-4, IL-17A or IL-22, major cytokines produced by Th1, Th2, Th17 or Th22 cells, respectively. IL-6 was also included in the transcriptional profile analysis because a variety of pro-inflammatory stimuli stimulate human keratinocytes to produce IL-6 that has an autocrine or paracrine role in epidermal immunity. We aimed to discover commonly expressed genes in human keratinocytes in response to pro-inflammatory cytokines, which would be associated with common pathophysiological responses in various skin diseases such as skin permeability barrier disruption or epidermal hyperplasia. Normal human keratinocytes (NHKs) were stimulated with IFNγ, IL-4, IL-6, IL-17A and IL-22 for 24 hours and harvested for total RNA extraction and hybridization on Affymetrix microarrays.

2014-10-02 | E-GEOD-53751 | biostudies-arrayexpress

A protective function of IL-22BP in acute liver injury

Project description:Acute liver injury is a critical life-threatening event. Common causes are infections, intoxication, and ischemic conditions. The cytokine Interleukin 22 (IL-22) has been implicated in this process. However, the role of IL-22 during acute liver damage is controversial, since both protective and pathogenic properties have been reported. IL-22 binding protein (IL-22BP, IL-22Ra2), a soluble endogenous inhibitor of IL-22, is able to regulate IL-22 activity, and thus might explain some of the controversial findings. Since the role of IL-22BP in liver injury is unknown, we used Il22bp deficient mice and mouse models for acute liver damage to address this point. We found that Il22bp deficient mice were more susceptible to ischemia- and acetaminophen- induced liver damage. Deficiency of Il22bp caused increased hepatic damage and delayed liver regeneration. Using an unbiased approach, we found that IL-22, if uncontrolled in Il22bp deficient mice, induced Cxcl10 expression by hepatocytes, thereby recruiting inflammatory CD11b+Ly6C+ monocytes into the liver upon liver damage. Accordingly, neutralization of Cxcl10 reversed the increased disease susceptibility of Il22bp deficient mice. In conclusion, our data suggest dual functions of IL-22 in acute liver damage, and highlight the need to control IL-22 activity via IL-22BP.

2017-12-22 | GSE93034 | GEO

IL-22 promotes cell proliferation to combat virus infection in human intestinal epithelial cells

Project description:Interferon lambdas (IFN-λs) are crucial to control virus infections at mucosal surfaces. Interleukin-22 (IL-22) was reported to help IFN-λ control rotavirus infection in mice either by aiding in the induction of interferon stimulated genes (ISGs) or by increasing cell proliferation thereby clearing virally infected cells. We investigated whether IL-22 and IFN-λs exhibited similar synergistic effects in human intestinal epithelial cells models. Our results showed that co-treatment of IL-22 and IFN-λ induced more phosphorylation of STAT1 than either cytokine used alone. However, this increased STAT1 activation did not translate to increased ISG production or antiviral protection. Transcriptomics analysis revealed that despite sharing a receptor and activating the similar STATs, the signaling generated by IL-22 and IFN-λs is independent where IFN-λs signaling induces ISGs and IL-22 signaling induces cell proliferation genes. Using human intestinal organoids, we confirmed that IL-22 increased the size of the organoids due to increased cell proliferation and increasing the stem cell marker (OLFM4). These findings suggest that in human intestinal cells, IFN-λs and IL-22 act independently to clear virus infections. IFN-λs induce ISGs to control virus replication and spread while IL-22 increases cell proliferation to eliminate infected cells and repair the damage epithelium. Although, these two cytokines do not increase each other’s function, they each play a key role in protecting human intestinal epithelium cells.

2023-12-30 | GSE243230 | GEO

Distinct Roles of IL-4, IL-13, and IL-22 in Human Skin Barrier Dysfunction and Atopic Dermatitis

Project description:Distinct Roles of IL-4, IL-13, and IL-22 in Human Skin Barrier Dysfunction and Atopic Dermatitis

| PRJNA1241732 | ENA

Gene expression profile of human epidermal keratinocytes in response to IFNgamma, IL-4, IL-6, IL-17A and IL-22

2014-10-02 | GSE53751 | GEO

G-Protein-Coupled Receptor 68 Negatively Regulates IL-22 Production in Human Th17 Cells

Project description:Purpose: To identify novel genes regulated by the aryl hydrocarbon receptor that influence human Th17 cell function. Methods: Naïve CD4 T cells from peripheral blood of six healthy human volunteers were cultured under four experimental conditions for three days: anti-CD3 and anti-CD28 antibodies (Media control), Media with Th17 conditions (IL-6, TGF-b, IL-1b, IL-23), Th17+FICZ and Th17+CH223191. Total RNA was extracted from each sample on day 3 and sequenced in a paired-end 2x50bp strategy on an Illumina HiSeq1500. A total of six donors were analyzed. Results: AhR activation with FICZ suppressed IL-17 production from human CD4 T cells and increased IL-22. AhR inhibition with CH223191 potently suppressed IL-22 and modestly increased IL-17 production. On day 3, the number of significantly regulated genes for each treatment were 975 (Th17), 88 (Th17+FICZ) and 142 (Th17+CH223191). 11 common genes were significantly regulated by all three treatments. One of these, GPR68, was investigated further in functional studies since its expression correlated with IL-22 production. Activation of GPR68 with a positive allosteric modulator suppressed IL-22 concentrations in human Th17 cell cultures. Conclusions: Our study demonstrates that GPR68 activation can negatively regulate IL-22 production from human CD4 T cells in the presence of an AhR agonist. RNA-seq is a powerful method to identify novel gene targets that regulate cytokines involved in chronic inflammatory diseases.

2018-07-19 | GSE102045 | GEO

Primary Human Bronchial Epithelial Cells (HBEs) Stimulated with IL-22 and IL-17

2008-01-23 | GSE10240 | GEO

Transcription profiling of primary human bronchial epithelial cells stimulated with IL-22 and IL-17

Project description:Primary HBE cells were stimulated with IL-22 and IL-17, and gene expression was studied using an Affymetrix platform microarray, in order to investigate which genes may be upregulated or downregulated in response to these cytokines. Of particular interest was the host defense genes such as antimicrobial peptides, which have been shown to be upregulated by IL-22 and IL-17 in skin keratinocytes. Experiment Overall Design: There were 4 conditions to this study (media, IL-22, IL-17 and IL-22+17) and there were 3 biological replicates of each condition. Experiment Overall Design: Gene expression study using one timepoint of 24 hours after stimulating these primary cells with the above conditions

2008-06-11 | E-GEOD-10240 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data