Progressive activation of TH2/TH22 cytokines and selective epidermal proteins characterizes acute and chronic atopic dermatitis
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Background Atopic dermatitis (AD) is a common disease with an increasing prevalence. The primary pathogenesis of the disease is still elusive, resulting in the lack of specific treatments. AD is currently considered a biphasic disease, with T(H)2 predominating in acute disease and a switch to T(H)1 characterizing chronic disease. Elucidation of the molecular factors that participate in the onset of new lesions and maintenance of chronic disease is critical for the development of targeted therapeutics.Objectives We sought to characterize the mechanisms underlying the onset and maintenance of AD.Methods We investigated intrapersonal sets of transcriptomes from nonlesional skin and acute and chronic lesions of 10 patients with AD through genomic, molecular, and cellular profiling.Results Our study associated the onset of acute lesions with a striking increase in a subset of terminal differentiation proteins, specifically the cytokine-modulated S100A7, S100A8, and S100A9. Acute disease was also associated with significant increases in gene expression levels of major T(H)22 and T(H)2 cytokines and smaller increases in IL-17 levels. A lesser induction of T(H)1-associated genes was detected in acute disease, although some were significantly upregulated in chronic disease. Further significant intensification of major T(H)22 and T(H)2 cytokines was observed between acute and chronic lesions.Conclusions Our data identified increased S100A7, S100A8, and S100A9 gene expression with AD initiation and concomitant activation of T(H)2 and T(H)22 cytokines. Our findings support a model of progressive activation of T(H)2 and T(H)22 immune axes from the acute to chronic phases, expanding the prevailing view of pathogenesis with important therapeutic implications.
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Circulating IL-22 correlates with AD severity and appears to be a key driver of the inflammatory reaction.
“Circulating IL-22 correlates with the severity of AD and appears as a key driver in the inflammatory reaction116,119.”
From Atopic dermatitis: an expanding therapeutic pipeline for a complex disease (2022) · cites this paper as [119]
The Results section on acute AD reports a positive correlation between lesional IL-22 mRNA and severity (SCORAD), but it was not statistically significant (r=0.55, P=0.132); it does not measure circulating IL-22. The Discussion proposes that IL-22 may contribute to epidermal changes, rather than establishing it as a key driver of inflammation. Page numbers are unavailable in our copy. (LLM, conf=0.88)
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- Authors
- Gittler, J. K., Shemer, A., Suárez-Fariñas, M., Fuentes-Duculan, J., Gulewicz, K. J., Wang, C. Q. F., Mitsui, H., Cardinale, I., de Guzman Strong, C., Krueger, J. G., & Guttman-Yassky, E.
- Affiliations
- Albert Einstein College of Medicine (US)
- Tel Aviv University (IL)
- Washington University in St. Louis (US)
- Rockefeller University (US)
- Venue
- Journal of Allergy and Clinical Immunology
- Publisher
- Elsevier BV
- Published
- 2012-12
- Volume
- 130
- Issue
- 6
- Pages
- 1344-1354
- ISSN
- 0091-6749 (ISSN-L)
- PMC
- PMC3991245
- OpenAlex
- W2002600662
- Cited by
- 981
- References
- 71
- Citations by year
- 2026: 72 · 2025: 82 · 2024: 83 · 2023: 106 · 2022: 76 · 2021: 93 · 2020: 86 · 2019: 84 · 2018: 67 · 2017: 76 · 2016: 53 · 2015: 51 · 2014: 32 · 2013: 15 · 2012: 2
- FWCI
- 39.99
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Allergy and Clinical Immunology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Amgen
- Eli Lilly and Company
- Pfizer
- Regeneron Pharmaceuticals
- National Institutes of Health (UL1TR000043)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R00AR055948)
- National Center for Research Resources (UL1RR024143)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
- Health Sciences › Medicine › Dermatology › Contact Dermatitis and Allergies
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Keywords
- atopic dermatitis, Th2 cytokines, S100A7, S100A8, S100A9, IL-17, Th1 cytokines, acute and chronic diseases, skin transcriptome, pathogenesis, disease progression
- MeSH terms
- S100 Calcium Binding Protein A7, Interleukin-22, Acute Disease, Adult, Aged, Chronic Disease, Dermatitis, Atopic, Female, Humans, Interleukins, Male, Middle Aged, S100 Proteins, Skin, Up-Regulation, Th2 Cells, Interleukin-17, Calgranulin A, Calgranulin B, Young Adult, Th1-Th2 Balance, Th17 Cells
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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