ArticleAllergy2026
Distinct Roles of IL-4, IL-13, and IL-22 in Human Skin Barrier Dysfunction and Atopic Dermatitis.
Article in Allergy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 2 of them syntheses that pooled it.
What it found
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The trial behind it
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Who cites it
24 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Dupilumab for the treatment of eczema molluscatum: A pediatric case report and systematic literature review.Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG · 2026Pooled it
- Impact of IL-4/IL-13 Blockade with Dupilumab on the Microbiome in Type 2 Inflammatory Diseases: A Systematic Review.Current allergy and asthma reports · 2026Pooled it
- Use of Tralokinumab in a Hairdresser With Severe Chronic Hand Eczema and Occupational Allergic Contact Dermatitis.Contact dermatitis · 2026Article
- OX40 Ligand/OX40 Axis as the Inflammatory Prequel in Atopic Dermatitis: A Narrative Review.Dermatology and therapy · 2026Review
- Article
- Rethinking Head and Neck Atopic Dermatitis: Pathogenic Axes and Emerging Therapeutic Directions.American journal of clinical dermatology · 2026Review
- Type-2-Inflammatory-Diseases Share Comorbidities, Molecular Signatures, IL4/IL13 Genetics, and Response to IL4/IL13 Blockade.Allergy · 2026Article
- Effects of Extended-Release Polyhexanide on Inflammatory Cytokine Expression and Disease Severity Following Staphylococcus Aureus Exposure in a Murine Dermatitis Model.Life (Basel, Switzerland) · 2026Article
- Single-cell transcriptomic analysis identifies a MIF-driven keratinocyte-macrophage-Th2 axis as a key inflammatory circuit in atopic dermatitis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Efficacy of Upadacitinib in Patients with Atopic Dermatitis of the Head and Neck Region.Dermatology and therapy · 2026Article
- Staphylococcus aureus Augments Epithelial Skin Barrier Damage Through T Cell Activation in Cutaneous T Cell Lymphoma.Allergy · 2026Article
- Rapid Human Skin Barrier Disruption by Sodium Dodecyl Sulfate and Associated Molecular Mechanisms.Allergy · 2026Article
- Atopic dermatitis.Nature reviews. Disease primers · 2026Review
- The Impact of the Exposome on Epithelial Barriers: New Approach Methodologies for Translational Research.Thoracic research and practice · 2026Article
- T Cell Immunosenescence in Inflammatory Skin Diseases: Pathogenesis and Therapeutic Targets.Aging cell · 2026Review
- Molecular Markers Distinguishing Early-Stage Mycosis Fungoides From Atopic Dermatitis Skin Lesions.Experimental dermatology · 2026Article
- Th2 Cytokines Reshape the Transcriptome: Insights from a Canine Organoid Model of Atopic Dermatitis.International journal of molecular sciences · 2026Article
- Article
- The neuro-immune insights of itch: peripheral mechanisms and central glial contributions.Cellular & molecular biology letters · 2026Review
- The potential of targeted IL-4 therapy for the comorbidity of atopic dermatitis and attention-deficit/hyperactivity disorder in children via the skin-brain axis.Frontiers in allergy · 2026Article
Corrections and comments
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Authors and funding
13 authors.
Funding
Abstract
backgroundAtopic dermatitis (AD) is a chronic type-2 inflammatory skin disease characterized by eczema and epithelial barrier dysfunction. Along with the type-2 cytokines IL-4 and IL-13, IL-22 contributes to AD pathogenesis. To date, most skin studies rely on reconstructed keratinocytes, which do not represent the real skin response.
objectiveHere, we report the distinct effects of IL-4, IL-13, and IL-22 on bio-stabilized human skin with intact barriers and immune cells.
methodsSpatial transcriptomics on AD-lesions and non-lesional skin was performed. Ex vivo skin barrier integrity was evaluated using electrical impedance spectroscopy (EIS), RNA-sequencing, and untargeted proteomics, complemented by analyses of skin biopsies from dupilumab-treated AD patients.
resultsSpatial transcriptomics demonstrated that AD lesions showed reduced expression of key barrier genes, including CLDN1, FLG, and FLG2. IL-4, IL-13, and IL-22 disrupted the skin barrier in the ex vivo human skin. Combining type-2 cytokines and IL-22 alone downregulated genes critical for barrier function and keratinization. In addition, IL-4 and IL-13 downregulated antimicrobial peptides, while IL-22 upregulated them. Interestingly, IL-4 and IL-13 reduced IL-22Rα1, and IL-22 upregulated IL-4Rα, suggesting immune cross-regulation. Proteomic analysis confirmed that all three cytokines (IL-4, IL-13, and IL-22) reduced the expression of key skin barrier proteins, particularly filaggrin and claudin-1. Dupilumab treatment of AD patients for 3 months restored IL-4/IL-13-dysregulated genes, whereas it had limited effect on IL22-associated pathways.
conclusionThis comprehensive study provides insights into the distinct immune profiles following IL-4, IL-13, and IL-22 stimulation on human skin, highlighting their complex interplay in disrupting skin barrier function and modulating innate immune responses.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.