Evidence map›Paper›PMID 40985485›Full record

ArticleAllergy2026

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

Paolo D'Avino, Juno Kim, Manru Li, Philipp Gessner, Patrick Westermann, Yagız Pat, Carina Beha, Claudia Traidl-Hoffmann, Jeremy Bost, Nicolas Gaudenzio and 3 more

Abstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed, 2 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

24 citing papers in PubMed, 2 syntheses or guidelines pooled it.

  1. 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 · 2026
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  9. 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.] · 2026
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  13. Atopic dermatitis.Nature reviews. Disease primers · 2026
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Paolo D'AvinoSwiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.
Juno KimSwiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.
Manru LiSwiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.
Philipp GessnerSwiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.
Patrick WestermannSwiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.
Yagız PatSwiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.
Carina BehaSwiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.ORCID https://orcid.org/0009-0000-2527-7178
Claudia Traidl-HoffmannCK CARE - Christine Kühne Center for Allergy Research and Education, Davos, Switzerland.ORCID https://orcid.org/0000-0001-5085-5179
Jeremy BostSciBase AB, Sundbyberg, Sweden.
Nicolas GaudenzioToulouse Institute for Infectious and Inflammatory Disease (Infinity), INSERM UMR1291, CNRS UMR5051, University Toulouse III, Toulouse, France.ORCID https://orcid.org/0000-0002-5648-509X
Christoph B MessnerSwiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.
Cezmi A AkdisSwiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.ORCID https://orcid.org/0000-0001-8020-019X
Yasutaka MitamuraSwiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.ORCID https://orcid.org/0000-0001-6389-9285

Funding

This work was funded by SciBase AB, GenoSkin SAS, and the Swiss National Foundation. SciBase AB contributed EIS instruments and electrodes for the study and contributed toward study funding. Genoskin SAS provided NativeSkin samples for the study with special discounts.
6 · The paper itself

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.

Indexed as

Dermatitis, AtopicInterleukin-13Interleukin-4InterleukinsSkinAdultFemaleFilaggrin ProteinsHumansInterleukin-22KeratinocytesProteomicsFilaggrin ProteinsFLG protein, humanIL13 protein, humanIL4 protein, humanInterleukin-13Interleukin-22Interleukin-4Interleukinsatopic dermatitisdupilumab (anti‐IL4Rα antibody)electrical impedance spectroscopyex vivo human skininflammationinterleukin‐13interleukin‐22interleukin‐4skin barrier

Identifiers

PMID40985485
PMCPMC12862561

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.