Atopic Dermatitis Is an IL-13–Dominant Disease with Greater Molecular Heterogeneity Compared to Psoriasis
Open accessAbstract
Atopic dermatitis (AD) affects up to 20% of children and adults worldwide. To gain a deeper understanding of the pathophysiology of AD, we conducted a large-scale transcriptomic study of AD with deeply sequenced RNA-sequencing samples using long (126-bp) paired-end reads. In addition to the comparisons against previous transcriptomic studies, we conducted in-depth analysis to obtain a high-resolution view of the global architecture of the AD transcriptome and contrasted it with that of psoriasis from the same cohort. By using 147 RNA samples in total, we found striking correlation between dysregulated genes in lesional psoriasis and lesional AD skin with 81% of AD dysregulated genes being shared with psoriasis. However, we described disease-specific molecular and cellular features, with AD skin showing dominance of IL-13 pathways, but with near undetectable IL-4 expression. We also demonstrated greater disease heterogeneity and larger proportion of dysregulated long noncoding RNAs in AD, and illustrated the translational impact, including skin-type classification and drug-target prediction. This study is by far the largest study comparing the AD and psoriasis transcriptomes using RNA sequencing and demonstrating the shared inflammatory components, as well as specific discordant cytokine signatures of these two skin diseases.
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IL-13 has been identified as the key TH2 cytokine mediating skin inflammation in AD.
“IL-13 has been identified as the key TH2 cytokine mediating the skin inflammation in AD88,89.”
From Atopic dermatitis: an expanding therapeutic pipeline for a complex disease (2022) · cites this paper as [88]
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- Authors
- Tsoi, L. C., Rodriguez, E., Degenhardt, F., Baurecht, H., Wehkamp, U., Volks, N., Szymczak, S., Swindell, W. R., Sarkar, M. K., Raja, K., Shao, S., Patrick, M., Gao, Y., Uppala, R., Perez White, B. E., Getsios, S., Harms, P. W., Maverakis, E., Elder, J. T., Franke, A., Gudjonsson, J. E., & Weidinger, S.
- Affiliations
- University of Michigan (US)
- University Hospital Schleswig-Holstein (DE)
- Christian-Albrechts-Universität zu Kiel (DE)
- Ohio University (US)
- Northwestern University (US)
- University of California Davis Medical Center (US)
- Corresponding author
- Gudjonsson, Johann E.
- ORCID
- Venue
- Journal of Investigative Dermatology
- Publisher
- Elsevier BV
- Published
- 2019-07
- Volume
- 139
- Issue
- 7
- Pages
- 1480-1489
- ISSN
- 0022-202X (ISSN-L)
- PMC
- PMC6711380
- OpenAlex
- W2908925106
- Cited by
- 469
- References
- 53
- Citations by year
- 2026: 65 · 2025: 63 · 2024: 76 · 2023: 79 · 2022: 64 · 2021: 56 · 2020: 47 · 2019: 17 · 2013: 1
- FWCI
- 46.40
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Investigative Dermatology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (EXC 22167-390884018)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR054966, AR060802, AR072129)
- Bundesministerium für Bildung und Forschung (01ZX1306A, 01ZX1510)
- Arthritis National Research Foundation
- Else Kröner-Fresenius-Stiftung (2014_A270)
- Dermatology Foundation
- National Psoriasis Foundation (GSE121212)
- A. Alfred Taubman Medical Research Institute
- National Institute of Allergy and Infectious Diseases (R01-AR06)
- Topics
- Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Health Sciences › Medicine › Dermatology › Contact Dermatitis and Allergies
- Keywords
- atopic dermatitis, psoriasis, transcriptome, IL-13, IL-4, long non-coding RNA, disease heterogeneity, dysregulated genes, cytokine signature, skin type classification, drug target prediction, lesional skin
- MeSH terms
- Dermatitis, Atopic, Humans, Organ Specificity, Psoriasis, RNA, Skin, Cohort Studies, Signal Transduction, Interleukin-4, Sequence Analysis, RNA, Th2 Cells, Interleukin-13, Gene Expression Profiling, Transcriptome, RNA, Long Noncoding
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