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 underlying the complex clinical phenotype are key to understanding the value of targeted therapies for distinct pathways such as TH2, TH17, and/or TH22.
“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]
The Results describe age-related differences in TH2, TH17 and TH22 markers, and the Discussion says these differences may inform the choice of targeted treatment. The paper does not establish sequential or cumulative immunological events underlying the clinical phenotype, or the value of therapies targeting each of the three pathways; it says the treatment implications require age-specific clinical trials. (LLM, conf=0.82)
Experimental — accuracy not yet measuredThere is increasing evidence that the IL-23-IL-17 axis and IL-36 may have a role in some AD subtypes, such as the intrinsic form and in Asian patients.
“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]
The Results and Discussion report elevated IL-17 and other TH17-related markers in atopic dermatitis, particularly in infants, supporting a possible role for that pathway. The passages do not establish a role for IL-36 or address the specified intrinsic and Asian patient subtypes; searches for those terms did not find relevant passages. The cited paper studies age groups rather than those subtypes. (LLM, conf=0.82)
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- 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 › Physiology › 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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