Dataset Information

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

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.

SUBMITTER: Tsoi LC

PROVIDER: S-EPMC6711380 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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

Tsoi Lam C LC Rodriguez Elke E Degenhardt Frauke F Baurecht Hansjörg H Wehkamp Ulrike U Volks Natalie N Szymczak Silke S Swindell William R WR Sarkar Mrinal K MK Raja Kalpana K Shao Shuai S Patrick Matthew M Gao Yilin Y Uppala Ranjitha R Perez White Bethany E BE Getsios Spiro S Harms Paul W PW Maverakis Emanual E Elder James T JT Franke Andre A Gudjonsson Johann E JE Weidinger Stephan S

The Journal of investigative dermatology 20190111 7

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 ...[more]

PMID: 30641038

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Project description:Recently, it was shown that lesional skin of atopic dermatitis patients expresses low levels of some antimicrobial peptides, compared with psoriasis patients. Here we performed microarray analysis on mRNA from purified lesional epidermal cells of patients with chronic plaque psoriasis and chronic atopic dermatitis, to investigate whether this is a general phenomenon for host defense proteins, and how specific it is for this class of molecules. We found overexpression of many antimicrobial genes in keratinocytes from psoriatic skin compared with atopic dermatitis skin. Interestingly, we observed that markers of normal differentiation and the activated/hyperproliferative epidermal phenotype were expressed at equal levels. Chronic lesions of psoriasis and atopic dermatitis patients are remarkably similar with respect to cellular proliferation. We conclude that psoriatic epidermis expresses high levels of host defense proteins compared with atopic dermatitis epidermis, and this phenomenon appears to be specific for these proteins. It remains to be investigated whether this is caused by genetic polymorphisms in pathways leading to an epidermal antimicrobial response, or by differences in the cellular infiltrate in psoriasis compared with atopic dermatitis. In general the microarray technique is used to probe a (very large) number of genes for say the deseased and the healthy state.Then gene ontology is used to detect the involved pathways.We did not set out to find a comprehensive list of genes involved in these skin deseases.We do suspect that the "path way" approach might be a bit anthropomorphic.Here we offered a different approach.We set out to investigate the evolutionary fitness changes from one local maximum , Psoriasis , to another , Atopie. Our hypothesis is that Psoriasis is at one extreme in the reaction of the evolution to invading micro organisms and Atopie at an other.So the vast chemical web called human being with numorous feedback and feed forward signals would then be tilted a bit in multidimensional Gene Space and the microarray technique would show us a glimpse of the involved genes. Keywords: Disease state analysis

Dataset Information

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

Publications

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

Similar Datasets

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