Evolution of pathologic T-cell subsets in patients with atopic dermatitis from infancy to adulthood
Open accessAbstract
Background The circulating immune phenotype was defined in adults and young children with early atopic dermatitis (AD), but chronologic changes in the blood of infants and children with AD through adolescence have not been explored.Objective We sought to compare immune activation and cytokine polarization in the blood of 0- to 5-year-old (n = 39), 6- to 11-year-old (n = 26), 12- to 17-year-old (n = 21) and 18-year-old or older (n = 43) patients with AD versus age-matched control subjects.Methods Flow cytometry was used to measure IFN-γ, IL-9, IL-13, IL-17, and IL-22 cytokine levels in CD4+/CD8+ T cells, with inducible costimulator molecule and HLA-DR defining midterm and long-term T-cell activation, respectively, within skin-homing/cutaneous lymphocyte antigen (CLA)+ versus systemic/CLA- T cells. Unsupervised clustering differentiated patients based on their blood biomarker frequencies.Results Although CLA+ T H 1 frequencies were significantly lower in infants with AD versus all older patients (P < .01), frequencies of CLA+ T H 2 T cells were similarly expanded across all AD age groups compared with control subjects (P < .05). After infancy, CLA- T H 2 frequencies were increased in patients with AD in all age groups, suggesting systemic immune activation with disease chronicity. IL-22 frequencies serially increased from normal levels in infants to highly significant levels in adolescents and adults compared with levels in respective control subjects (P < .01). Unsupervised clustering aligned the AD profiles along an age-related spectrum from infancy to adulthood (eg, inducible costimulator molecule and IL-22).Conclusions The adult AD phenotype is achieved only in adulthood. Unique cytokine signatures characterizing individual pediatric endotypes might require age-specific therapies. Future longitudinal studies, comparing the profile of patients with cleared versus persistent pediatric AD, might define age-specific changes that predict AD clearance.
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There 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 [124]
The Discussion reports an IL-17 signature in pediatric atopic dermatitis skin, providing limited support for a role for IL-17 in a subtype of the disease. It does not establish a role for the IL-23–IL-17 axis or IL-36, or address the intrinsic form or Asian patients; searches for those terms found no relevant passage. The cited copy provides no page numbers. (LLM, conf=0.78)
Experimental — accuracy not yet measuredThe 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 [124]
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Emerging trends in clinical research on Janus kinase inhibitors for atopic dermatitis treatment
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Elevation of IgE in patients with psoriasis: Is it a paradoxical phenomenon?
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Considerations for managing elderly patients with atopic dermatitis
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Latest Progresses in Allergic Diseases Biomarkers: Asthma and Atopic Dermatitis
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Cytotoxic T Cells: Kill, Memorize, and Mask to Maintain Immune Homeostasis
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Shedding light on key pharmacological knowledge and strategies for pediatric atopic dermatitis
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Self-citationInterleukin antagonists for atopic dermatitis: a new era of therapy
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Self-citationOral Administration of Apple Pectin Solution Improves Atopic Dermatitis in a Mouse Model
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Implication of T Helper Cytokines in Contact Dermatitis and Atopic Dermatitis
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Self-citationEpigenetic and Transcriptional Dysregulation in T cells of Patients with Atopic Dermatitis
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Self-citationCirculating CLA+ Memory T Cells in Skin Diseases: A Translational Perspective
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Self-citationAtopic Multimorbidity in Adults With a Focus on Sensitization Patterns and T Cell Activation
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Self-citationExpert opinion on management of moderate-to-severe atopic dermatitis in Qatar
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Atopic Dermatitis Immune Dysregulation as Dengue Predisposing Factor
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Temporal and Topographical Heterogeneities in Clinical Manifestations of Atopic Dermatitis in China
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Self-citationDNA methylation-based analysis of leukocyte landscape in children with atopic dermatitis
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Untangling the Complexity of Childhood Atopic Dermatitis: Phenotypes and Endotypes
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Hand eczema leaves systemic traces
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- Authors
- Czarnowicki, T., He, H., Canter, T., Han, J., Lefferdink, R., Erickson, T., Rangel, S., Kameyama, N., Kim, H. J., Pavel, A. B., Estrada, Y., Krueger, J. G., Paller, A. S., & Guttman-Yassky, E.
- Affiliations
- Rockefeller University (US)
- Icahn School of Medicine at Mount Sinai (US)
- Northwestern University (US)
- ORCID
- Venue
- Journal of Allergy and Clinical Immunology
- Publisher
- Elsevier BV
- Published
- 2020-01
- Volume
- 145
- Issue
- 1
- Pages
- 215-228
- ISSN
- 0091-6749 (ISSN-L)
- PMC
- PMC6957229
- OpenAlex
- W2980556682
- Cited by
- 118
- References
- 90
- Citations by year
- 2026: 9 · 2025: 22 · 2024: 19 · 2023: 19 · 2022: 17 · 2021: 22 · 2020: 10
- FWCI
- 12.34
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Journal of Allergy and Clinical Immunology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Seoul National University Open Repository (Seoul National University) (submittedVersion)
- Funders
- National Institute of Arthritis and Musculoskeletal and Skin Diseases
- Topics
- Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
- Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Keywords
- atopic dermatitis, T cell subsets, age-related immune changes, cutaneous lymphocyte antigen, skin-homing T cells, Th1/Th2 balance, IL-22, IL-13, IL-17, IL-9, interferon-gamma, HLA-DR, T cell activation, chronicity, infants and children
- MeSH terms
- Adolescent, Adult, Child, Child, Preschool, Dermatitis, Atopic, Female, HLA-DR Antigens, Humans, Infant, Infant, Newborn, Male, Cytokines, Th1 Cells, Th2 Cells
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