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The molecular features of normal and atopic dermatitis skin in infants, children, adolescents, and adults
Open accessAbstract
Background Although atopic dermatitis (AD) often presents in infancy and persists into adulthood, comparative characterization of AD skin among different pediatric age groups is lacking.Objective We sought to define skin biopsy profiles of lesional and nonlesional AD across different age groups (0-5-year-old infants with disease duration <6 months, 6-11-year-old children, 12-17-year-old adolescents, ≥18-year-old adults) versus age-appropriate controls.Methods We performed gene expression analyses by RNA-sequencing and real-time PCR (RT-PCR) and protein expression analysis using immunohistochemistry.Results T H 2/T H 22 skewing, including IL-13, CCL17/thymus and activation-regulated chemokine, IL-22, and S100As, characterized the common AD signature, with a global pathway-level enrichment across all ages. Nevertheless, specific cytokines varied widely. For example, IL-33, IL-1RL1/IL-33R, and IL-9, often associated with early atopic sensitization, showed greatest upregulations in infants. T H 17 inflammation presented a 2-peak curve, with highest increases in infants (including IL-17A and IL-17F), followed by adults. T H 1 polarization was uniquely detected in adults, even when compared with adolescents, with significant upregulation in adults of IFN-γ and CXCL9/CXCL10/CXCL11. Although all AD age groups had barrier abnormalities, only adults had significant decreases in filaggrin expression. Despite the short duration of the disease, infant AD presented robust downregulations of multiple barrier-related genes in both lesional and nonlesional skin. Clinical severity scores significantly correlated with T H 2/T H 22-related markers in all pediatric age groups.Conclusions The shared signature of AD across ages is T H 2/T H 22-skewed, yet differential expression of specific T H 2/T H 22-related genes, other T H pathways, and barrier-related genes portray heterogenetic, age-specific molecular fingerprints.
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“The sequential and/or cumulative immunological events that underlie the complex clinical phenotype are key to understanding the value of targeted therapies for distinct pathways such as TH2, TH17 and/or TH22 response124,125.”
From Atopic dermatitis: an expanding therapeutic pipeline for a complex disease (2022) · cites this paper as [125]
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“there is increasing evidence that the IL-23–IL-17 axis as well as IL-36 (see above) may have a role, at least in some AD subtypes such as the so-called intrinsic form and in Asian patients73,103,117,123–125.”
From Atopic dermatitis: an expanding therapeutic pipeline for a complex disease (2022) · cites this paper as [125]
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Interleukin 31, a cytokine produced by activated T cells, induces dermatitis in mice
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Self-citationInterleukin‐33 ( IL ‐33): A nuclear cytokine from the IL ‐1 family
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Tight junction defects in patients with atopic dermatitis
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Research works printed but not linked: 1
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Self-citationTwo Phase 3 Trials of Lebrikizumab for Moderate-to-Severe Atopic Dermatitis
Silverberg, J. I., Guttman‐Yassky, E., Thaçi, D., Irvine, A. D., Gold, L. S., Blauvelt, A., Simpson, E. L., Chu, C., Liu, Z., Lima, R. G., et al. (2023) · New England Journal of Medicine · doi:10.1056/nejmoa2206714 · Cited by 363
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Metadata
- Authors
- Renert-Yuval, Y., Del Duca, E., Pavel, A. B., Fang, M., Lefferdink, R., Wu, J., Diaz, A., Estrada, Y. D., Canter, T., Zhang, N., Wagner, A., Chamlin, S., Krueger, J. G., Guttman-Yassky, E., & Paller, A. S.
- Affiliations
- University of Mississippi (US)
- Northwestern University (US)
- Icahn School of Medicine at Mount Sinai (US)
- Rockefeller University (US)
- Corresponding author
- Paller, Amy S.
- ORCID
- Venue
- Journal of Allergy and Clinical Immunology
- Publisher
- Elsevier BV
- Published
- 2021-07
- Volume
- 148
- Issue
- 1
- Pages
- 148-163
- ISSN
- 0091-6749 (ISSN-L)
- PMC
- PMC9285652
- OpenAlex
- W3120289132
- Cited by
- 168
- References
- 96
- Citations by year
- 2026: 23 · 2025: 37 · 2024: 38 · 2023: 35 · 2022: 23 · 2021: 12
- FWCI
- 24.00
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Allergy and Clinical Immunology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- Funders
- Feinberg School of Medicine
- Rockefeller University
- Topics
- Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
- Health Sciences › Medicine › Dermatology › Contact Dermatitis and Allergies
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Asthma and respiratory diseases
- Keywords
- atopic dermatitis, age differences, skin transcriptome, IL-13, IL-22, IL-33, IL-9, Th17 inflammation, Th1 polarization, skin barrier genes, filaggrin, disease severity, infants, children, adolescents, adults
- MeSH terms
- Filaggrin Proteins, Adolescent, Adult, Child, Dermatitis, Atopic, Eczema, Female, Humans, Infant, Inflammation, Male, Severity of Illness Index, Skin, Biomarkers, Cytokines, Th2 Cells, Young Adult
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