Atopic Dermatitis Is an IL-13-Dominant Disease with Greater Molecular Heterogeneity Compared to Psoriasis

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 comparis...

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Published in:Journal of investigative dermatology Vol. 139; no. 7; p. 1480
Main Authors: Tsoi, Lam C, Rodriguez, Elke, Degenhardt, Frauke, Baurecht, Hansjörg, Wehkamp, Ulrike, Volks, Natalie, Szymczak, Silke, Swindell, William R, Sarkar, Mrinal K, Raja, Kalpana, Shao, Shuai, Patrick, Matthew, Gao, Yilin, Uppala, Ranjitha, Perez White, Bethany E, Getsios, Spiro, Harms, Paul W, Maverakis, Emanual, Elder, James T, Franke, Andre, Gudjonsson, Johann E, Weidinger, Stephan
Format: Journal Article
Language:English
Published: United States 01.07.2019
Subjects:
Cohort Studies
Dermatitis, Atopic - genetics
Dermatitis, Atopic - immunology
Gene Expression Profiling
Humans
Interleukin-13 - genetics
Interleukin-13 - metabolism
Interleukin-4 - metabolism
Organ Specificity - genetics
Psoriasis - genetics
Psoriasis - immunology
RNA - genetics
RNA, Long Noncoding - genetics
Sequence Analysis, RNA
Signal Transduction
Skin - metabolism
Skin - pathology
Th2 Cells - immunology
Transcriptome
ISSN:1523-1747, 1523-1747
Online Access:Get more information
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Summary: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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ISSN:1523-1747
1523-1747
DOI:10.1016/j.jid.2018.12.018