Abstract
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.
| Original language | English |
|---|---|
| Journal | Journal of Investigative Dermatology |
| Volume | 139 |
| Issue number | 7 |
| Pages (from-to) | 1480-1489 |
| Number of pages | 10 |
| ISSN | 0022-202X |
| DOIs | |
| Publication status | Published - 07.2019 |
Funding
This work was supported by an award from the Else Kröner-Fresenius-Stiftung (2014_A270) (SW, ER), by the Deutsche Forschungsgemeinschaft (German Research Foundation) under Germany’s excellence Strategy–EXC 22167-390884018, by grants from the German Federal Ministry of Education and Research (BMBF) within the framework of the e:Med research and funding concept (sysINFLAME, grant 01ZX1306A) and the ComorbSysMed, grant 01ZX1510 (SS), and by the Babcock Endowment Fund (LCT, MKS, JT, JEG), by the National Institute of Arthritis and Musculoskeletal and Skin Diseases: AR060802 (JEG), AR054966 (JTE), and AR072129 (LCT), and National Institute of Allergy and Infectious Diseases under Award Number R01-AR06 (JEG), and the A. Alfred Taubman Medical Research Institute Kenneth and Frances Eisenberg Emerging Scholar Award (JEG). LCT is supported by the Dermatology Foundation, Arthritis National Research Foundation, and National Psoriasis Foundation.
