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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 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]
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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 [124]
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Self-citationInterleukin antagonists for atopic dermatitis: a new era of therapy
Tsiogka, A., Paschou, E., Koumaki, D., Vakirlis, E., & Gregoriou, S. (2024) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2024.2347294 · Cited by 5
Kim, H. S., Ahn, J. W., Ha, N. R., Damodar, K., Jang, S. K., Yoo, Y., Gyoung, Y. S., & Joo, S. S. (2024) · Marine Drugs · doi:10.3390/md22080354 · Cited by 5
Self-citationOral Administration of Apple Pectin Solution Improves Atopic Dermatitis in a Mouse Model
FUJISAKI, A., MATSUI, A., SHIKI, K., TATEISHI, R., & Itoh, T. (2024) · Journal of Nutritional Science and Vitaminology · doi:10.3177/jnsv.70.9 · Cited by 4
Cork, M. J., Ong, P. Y., Danby, S. G., Byers, R. A., Matcher, S. J., Katibi, O. S., Brown, K., Andrew, P. V., Pinnock, A., Poyner, A., et al. (2026) · Annals of Allergy Asthma & Immunology · doi:10.1016/j.anai.2026.01.008 · Cited by 3
Implication of T Helper Cytokines in Contact Dermatitis and Atopic Dermatitis
Cochez, P. M., Choteau, M., Limaye, N., Baeck, M., & Dumoutier, L. (2020) · Current Treatment Options in Allergy · doi:10.1007/s40521-020-00263-x · Cited by 3
Brooks, S. G., Lopez, L. M., Mashoudy, K. D., Yosipovitch, G., & Czarnowicki, T. (2024) · Dermatitis · doi:10.1089/derm.2024.0261 · Cited by 3
Self-citationEpigenetic and Transcriptional Dysregulation in T cells of Patients with Atopic Dermatitis
Eapen, A., Parameswaran, S., Forney, C. R., Edsall, L., Miller, D., Donmez, O. A., Dunn, K., Lu, X., Granitto, M., Rowden, H., et al. (2022) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2021.12.059 · Cited by 3
Czarnowicki, T., David, E., Yamamura, K., Han, J., He, H., Pavel, A. B., Glickman, J. W., Erickson, T. R., Estrada, Y. D., Krueger, J. G., et al. (2024) · Allergy · doi:10.1111/all.16225 · Cited by 3
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
Bialas, A., Rabe, M., Artz, N., Boldt, A., Simon, J. C., Treudler, R., & Klein, B. (2025) · Clinical and Translational Allergy · doi:10.1002/clt2.70129 · Cited by 2
Yamamura, K., Dahabreh, D., DUCA, E. D., Lozano‐Ojalvo, D., Kim, M., Murai‐Yamamura, M., Garcet, S., Gonzalez, J., Miura, S., Williams, S. C., et al. (2026) · Allergy · doi:10.1111/all.70252 · Cited by 2
Self-citationCzarnowicki, T., Sugita, K., Yiu, Z. Z. N., Díez-Ribas, S., García‐Jiménez, I., Guttman‐Yassky, E., & Santamaria‐Babí, L. F. (2026) · Allergy · doi:10.1111/all.70347 · Cited by 2
Self-citationExpert opinion on management of moderate-to-severe atopic dermatitis in Qatar
Steinhoff, M. S., Adeli, M., Riad, H., Allam, M., Hazem, A., Alsmadi, R., Kamal, A. M., Ibrahim, W., & Al‐Nesf, M. A. (2023) · Journal of Dermatological Treatment · doi:10.1080/09546634.2023.2251622 · Cited by 2
Atopic Dermatitis Immune Dysregulation as Dengue Predisposing Factor
Astuti, R. D. I., Alam, A., Ghozali, M., & Setiabudiawan, B. (2024) · Journal of Inflammation Research · doi:10.2147/jir.s493946 · Cited by 2
Temporal and Topographical Heterogeneities in Clinical Manifestations of Atopic Dermatitis in China
Li, Z., Yin, H., Wang, Y., Wang, S., Wu, Y., Qiu, Z., Yao, X., Gu, C., & Li, W. (2025) · Journal of Clinical Medicine · doi:10.3390/jcm14030840 · Cited by 2
Jeong, S., Shin, S., Choi, H. S., Choi, S., Jang, S., Song, J., Lee, J. S., Lee, D. H., Kim, H. J., Kim, J., et al. (2025) · Immune Network · doi:10.4110/in.2025.25.e26 · Cited by 2
Self-citationDNA methylation-based analysis of leukocyte landscape in children with atopic dermatitis
Jeremian, R., Li, K., Galati, M. A., Gooderham, M., Sibbald, C. J., Asai, Y., Piguet, V., & Jack, C. S. (2025) · Archives of Dermatological Research · doi:10.1007/s00403-025-04018-z · Cited by 1
Untangling the Complexity of Childhood Atopic Dermatitis: Phenotypes and Endotypes
Dumycz, K., Zygadło, J., Marzec, A., Strus, P., Kulus, M., Sokołowska, M., Venter, C., Leung, D. Y. M., & Feleszko, W. (2026) · Clinical Reviews in Allergy & Immunology · doi:10.1007/s12016-025-09128-0 · Cited by 2
Murashkin, N. N., Opryatin, L. A., Pavlova, E. S., Epishev, R. V., Materikin, A. I., Ivanov, R. A., Savelova, A. A., & Leonova, M. A. (2023) · Вопросы современной педиатрии · doi:10.15690/vsp.v22i5.2622 · Cited by 2
Hand eczema leaves systemic traces
Roesner, L. M., & Wittmann, M. (2023) · British Journal of Dermatology · doi:10.1093/bjd/ljad178 · Cited by 1
Atopic dermatitis in children: up to date insight on development and trends in therapy
Балаболкин, И. И. (2020) · Russian Pediatric Journal · doi:10.18821/1560-9561-2020-23-4-265-270
Ozdogan, E., & Arıkan, Ç. (2021) · The American Journal of Gastroenterology · doi:10.14309/ajg.0000000000001253
Metadata
- 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 › Pulmonary and Respiratory Medicine › 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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