IL 22 Human
Description
Cellular Sources and Production
IL-22 is secreted by multiple immune cell populations:
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Innate Immune Cells: Group 3 innate lymphoid cells (ILC3s), NK cells, and neutrophils .
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Inducers: IL-23, microbial ligands (e.g., LPS), and STAT3-activating cytokines .
Biological Functions
IL-22 exhibits context-dependent roles in homeostasis and disease:
Protective Roles
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Mucosal Defense: Upregulates antimicrobial peptides (e.g., Reg3β, defensins) in epithelial cells .
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Tissue Repair: Enhances epithelial cell survival and proliferation in the liver, lung, and gut .
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Metabolic Regulation: Modulates lipid metabolism and acute-phase protein synthesis .
Pathological Roles
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Autoimmunity: Drives inflammation in psoriasis, rheumatoid arthritis, and COPD .
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Cancer: Dual role in tumorigenesis—promotes hepatocellular carcinoma but inhibits colorectal cancer progression .
Research Trends and Key Findings (2014–2023)
A 2024 bibliometric analysis of 3,943 publications highlights:
Key discoveries include IL-22's role in cigarette smoke-induced COPD pathogenesis and its therapeutic potential in inflammatory bowel disease (IBD) .
Pathological Mechanisms in Disease Models
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COPD: IL-22 deficiency reduces neutrophilic inflammation and emphysema in murine models .
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Pancreatitis: IL-22 upregulates anti-apoptotic genes (e.g., Reg III) to mitigate tissue damage .
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Intestinal Inflammation: Enhances claudin-2 expression, increasing barrier permeability and pathogen clearance .
Future Directions
Current research focuses on:
Product Specs
(a) Reverse-Phase High-Performance Liquid Chromatography (RP-HPLC) analysis.
(b) Sodium Dodecyl Sulfate-Polyacrylamide Gel Electrophoresis (SDS-PAGE) analysis.
Q&A
What cells produce IL-22 in humans and how does this differ from mice?
| Cell Type | Human IL-22 Production | Mouse IL-22 Production | Key Differences |
|---|---|---|---|
| T helper cells | Produced by Th1, Th17, and distinct Th22 subset | Primarily driven by Th1 and Th17 cells | Humans have a distinct Th22 subset not found in mice |
| Th17 cells | Only small subset produces IL-22 | Larger proportion produces IL-22 | Different regulation in humans |
| Th22 cells | Produce IL-22 and TNFα, but neither IL-17 nor IFNγ | No distinct Th22 subset | Human-specific subset |
| Innate cells | ILC3s, NK cells, macrophages (including alveolar) | Similar distribution | Similar profile |
| Other sources | NKT cells, Tc-cell subsets, γδ T cells | Similar distribution | Similar profile |
Human Th22 cells were initially characterized in skin and represent a unique subset that distinguishes human IL-22 biology from murine models .
What is the molecular structure of human IL-22 and how does it function?
The crystallographic structure of recombinant human IL-22 has been solved at 2.0 Å resolution using the SIRAS (Single Isomorphous Replacement with Anomalous Scattering) method. Unlike IL-10, which forms an interpenetrated homodimer where secondary-structure elements from two polypeptide chains intertwine, human IL-22 dimerizes through interface interactions between monomers .
This structural difference has functional implications:
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While IL-10 requires a homodimer for signaling, human IL-22 most likely interacts with its receptor as a monomer
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Human IL-22 activates signal transducers and activators of transcription factors 1 and 3
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It induces acute phase reactants in hepatoma cell lines, suggesting involvement in inflammatory responses
What are the major downstream effects of IL-22 signaling in human tissues?
IL-22 serves as a crucial regulator of tissue responses during inflammation, with effects including:
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Activation of STAT1 and STAT3 signaling pathways
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Induction of epithelial cell proliferation and survival
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Stimulation of antimicrobial peptide production
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Promotion of tissue repair mechanisms
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Modulation of inflammatory responses in barrier tissues
IL-22 exhibits a dual nature in inflammatory conditions, acting either as a protective or inflammatory mediator depending on the disease context. It is upregulated in numerous chronic inflammatory diseases, including psoriasis, rheumatoid arthritis, and inflammatory bowel disease .
How do TGF-β signaling pathways regulate IL-22 production in human T cells?
TGF-β signaling demonstrates complex, context-dependent effects on IL-22 production in human T cells:
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In human samples, addition of TGF-β1 increases expression of both IL-22 and IL-17A
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TGF-β1 is essential for maintaining IL-17A expression in differentiated Th17 cells
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TGF-β1 and AhR (aryl hydrocarbon receptor) signaling together are crucial for Th17 cells to acquire IL-22 production capacity in vitro
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The relationship is cell subset-dependent:
The addition of AhR ligand (FICZ) together with TGF-β1 significantly enhances IL-22 production, while AhR inhibition strongly reduces the frequency of IL-17+IL-22+ cells. This indicates a cooperative mechanism between these two signaling pathways in regulating IL-22 expression .
What methodologies are most effective for measuring IL-22 in human samples?
Several complementary techniques are available for IL-22 detection in human samples:
| Methodology | Application | Advantages | Considerations | Protocol Details |
|---|---|---|---|---|
| ELISA | Quantification in serum, plasma, supernatants | High sensitivity for single analyte | Limited to one cytokine per assay | Commercial kits available specifically for human IL-22 |
| Cytometric Bead Array (CBA) | Multiplex detection in limited samples | Simultaneous detection of multiple cytokines | Requires flow cytometer | Dilute samples 1:100; incubate with mixed beads for 2h at RT |
| Flow Cytometry | Intracellular detection in specific cell populations | Cell-specific analysis, multi-parameter | Requires cell permeabilization | Human antibody: IL-22-PE, 22URTI, eBioscience (1:200) |
| Real-time PCR | Gene expression analysis | Sensitive measurement of transcription | mRNA may not correlate with protein | Human primers available: Il22 Mm01226722_g1 |
| TGFβ ImmunoAssay | Measuring related TGFβ levels | Detects both active and latent TGFβ | Requires acid activation for total TGFβ | TGFβ1 Emax ImmunoAssay System (Promega) |
When analyzing human samples, researchers should consider combining protein-level detection methods (ELISA/CBA) with gene expression analysis (PCR) for a comprehensive understanding of IL-22 biology .
How can researchers generate reliable IL-22 reporter systems for mechanistic studies?
Based on methodologies described in the literature, researchers have developed sophisticated reporter systems to track IL-22 expression. One approach is the generation of fluorescent protein reporter mice:
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Design a targeting vector containing:
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A short arm of the Il22 gene (e.g., 2.9 kb)
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An internal ribosomal entry site (IRES, ~640 bp)
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Gene encoding fluorescent protein (e.g., BFP, 735 bp)
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Selection marker (e.g., floxed neomycin gene)
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Long arm encoding the 3' end of Il22
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Insert the construct into the 3' untranslated region (UTR) of the Il22 gene to ensure:
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Reporter expression faithfully follows IL-22 expression
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No disruption of endogenous IL-22 expression
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Retention of normal regulation mechanisms
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Validate reporter fidelity:
While this approach has been implemented in mice, similar principles could be applied to human cell lines using CRISPR/Cas9 technology to create reporter systems for studying IL-22 regulation in human cells.
What are the current trends and emerging hotspots in human IL-22 research?
According to bibliometric analysis of IL-22 research from 2014 to 2023, several key trends have emerged:
| Research Area | Key Institutions | Leading Journals | Notable Contributors |
|---|---|---|---|
| Basic IL-22 biology | INSERM, University of California | Frontiers in Immunology | Guttman Yassky, E. |
| IL-22 in inflammatory diseases | US & Chinese institutions | Journal of Immunology | Multiple authors |
| Therapeutic applications | Academic & pharmaceutical collaborations | Various clinical journals | Diverse authorship |
The field has shown steady growth, with 3,943 articles published by 25,134 authors from 4,206 institutions across 106 countries during this period. The United States and China lead research output, with INSERM and the University of California system being the most productive institutions .
Current emerging research hotspots include:
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Elucidating the dual nature of IL-22 (protective vs. inflammatory)
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Developing IL-22-based therapeutic approaches
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Understanding IL-22's role in microbiome-host interactions
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Investigating IL-22 in cancer biology and immunotherapy
How should researchers design experiments to investigate contradictory IL-22 functions?
Given IL-22's dual nature as both protective and pathogenic in different contexts, experimental design requires careful consideration:
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Comprehensive cellular profiling:
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Analyze multiple cell types simultaneously (T cells, ILCs, macrophages)
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Use multi-parameter flow cytometry with antibody panels including:
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IL-17A-BV421, IL-22-PE, TNF-α-BV605, IFN-γ-BV786
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CD3-BUV737, CD4-PECy7, CD45-PECy5
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Sort specific cell populations for detailed transcriptomic analysis
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Context-dependent signaling analysis:
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Compare IL-22 effects in different tissue environments
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Analyze TGF-β levels in correlation with IL-22 function
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Investigate AhR pathway activation and its influence on IL-22 outcomes
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Time-course experiments:
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Analyze IL-22 production and effects at different disease stages
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Track dynamic changes in IL-22 signaling during inflammatory processes
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Combinatorial cytokine manipulation:
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Translational approaches:
Product Science Overview
Human recombinant IL-22 (hIL-22) is typically produced in human 293 cells. The recombinant protein is often lyophilized from a filtered solution of phosphate-buffered saline (PBS) and can be reconstituted for use in various assays . The molecular weight of nonglycosylated hIL-22 is approximately 16,749 Da, but due to glycosylation, it migrates as a 34 kDa polypeptide in SDS-PAGE .
IL-22 plays a crucial role in mediating proinflammatory responses, driving the production of antimicrobial peptides, and contributing to tissue repair and wound healing . It exerts its effects by binding to a heterodimeric receptor composed of IL-22R1 and IL-10R2 . The IL-22 receptor is predominantly expressed on tissue-resident cells, particularly those of epithelial origin .
Upon binding to its receptor, IL-22 activates several signaling pathways, including the JAK-STAT pathway (primarily STAT3), as well as the MEK-ERK-RSK, JNK-SAPK, and p38 pathways . These signaling cascades lead to various cellular responses, including the production of antimicrobial peptides and the promotion of cell survival and proliferation .
IL-22 has been studied for its potential therapeutic applications, particularly in the context of epithelial repair and protection against tissue injury . It has shown promise in preclinical models of liver, pancreas, gut, kidney, and lung injuries . Additionally, IL-22 plays a role in host defense against bacterial infections .
The therapeutic potential of IL-22 is further highlighted by its minimal side effects, as it specifically targets epithelial cells without affecting immune cells . Clinical studies have explored the use of IL-22-Fc fusion proteins to enhance its stability and efficacy in vivo .
