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
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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.
AbstractList	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. 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.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.
Author	Degenhardt, Frauke Harms, Paul W Volks, Natalie Swindell, William R Patrick, Matthew Franke, Andre Gao, Yilin Shao, Shuai Getsios, Spiro Rodriguez, Elke Baurecht, Hansjörg Szymczak, Silke Gudjonsson, Johann E Perez White, Bethany E Maverakis, Emanual Raja, Kalpana Tsoi, Lam C Wehkamp, Ulrike Elder, James T Weidinger, Stephan Uppala, Ranjitha Sarkar, Mrinal K
Author_xml	– sequence: 1 givenname: Lam C surname: Tsoi fullname: Tsoi, Lam C organization: Department of Dermatology, University of Michigan Medical School, Ann Arbor, Michigan, USA; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan, USA; Department of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan, USA – sequence: 2 givenname: Elke surname: Rodriguez fullname: Rodriguez, Elke organization: Department of Dermatology and Allergy, University Hospital Schleswig-Holstein, Kiel, Germany – sequence: 3 givenname: Frauke surname: Degenhardt fullname: Degenhardt, Frauke organization: Institute of Clinical Molecular Biology, University Hospital Schleswig-Holstein, Kiel, Germany – sequence: 4 givenname: Hansjörg surname: Baurecht fullname: Baurecht, Hansjörg organization: Department of Dermatology and Allergy, University Hospital Schleswig-Holstein, Kiel, Germany – sequence: 5 givenname: Ulrike surname: Wehkamp fullname: Wehkamp, Ulrike organization: Department of Dermatology and Allergy, University Hospital Schleswig-Holstein, Kiel, Germany – sequence: 6 givenname: Natalie surname: Volks fullname: Volks, Natalie organization: Department of Dermatology and Allergy, University Hospital Schleswig-Holstein, Kiel, Germany – sequence: 7 givenname: Silke surname: Szymczak fullname: Szymczak, Silke organization: Institute of Medical Informatics and Statistics, Kiel University, Kiel, Germany – sequence: 8 givenname: William R surname: Swindell fullname: Swindell, William R organization: Heritage College of Osteopathic Medicine, Ohio University, Athens, Ohio, USA – sequence: 9 givenname: Mrinal K surname: Sarkar fullname: Sarkar, Mrinal K organization: Department of Dermatology, University of Michigan Medical School, Ann Arbor, Michigan, USA – sequence: 10 givenname: Kalpana surname: Raja fullname: Raja, Kalpana organization: Department of Dermatology, University of Michigan Medical School, Ann Arbor, Michigan, USA – sequence: 11 givenname: Shuai surname: Shao fullname: Shao, Shuai organization: Department of Dermatology, University of Michigan Medical School, Ann Arbor, Michigan, USA – sequence: 12 givenname: Matthew surname: Patrick fullname: Patrick, Matthew organization: Department of Dermatology, University of Michigan Medical School, Ann Arbor, Michigan, USA – sequence: 13 givenname: Yilin surname: Gao fullname: Gao, Yilin organization: Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan, USA – sequence: 14 givenname: Ranjitha surname: Uppala fullname: Uppala, Ranjitha organization: Department of Dermatology, University of Michigan Medical School, Ann Arbor, Michigan, USA – sequence: 15 givenname: Bethany E surname: Perez White fullname: Perez White, Bethany E organization: Department of Dermatology, Northwestern University, Chicago, Illinois, USA – sequence: 16 givenname: Spiro surname: Getsios fullname: Getsios, Spiro organization: Department of Dermatology, Northwestern University, Chicago, Illinois, USA – sequence: 17 givenname: Paul W surname: Harms fullname: Harms, Paul W organization: Department of Dermatology, University of Michigan Medical School, Ann Arbor, Michigan, USA – sequence: 18 givenname: Emanual surname: Maverakis fullname: Maverakis, Emanual organization: Department of Dermatology, School of Medicine, UC Davis Medical Center, Sacramento, California, USA – sequence: 19 givenname: James T surname: Elder fullname: Elder, James T organization: Department of Dermatology, University of Michigan Medical School, Ann Arbor, Michigan, USA; Ann Arbor Veterans Affairs Hospital, Ann Arbor, Michigan, USA – sequence: 20 givenname: Andre surname: Franke fullname: Franke, Andre organization: Institute of Clinical Molecular Biology, University Hospital Schleswig-Holstein, Kiel, Germany – sequence: 21 givenname: Johann E surname: Gudjonsson fullname: Gudjonsson, Johann E email: johanng@med.umich.edu organization: Department of Dermatology, University of Michigan Medical School, Ann Arbor, Michigan, USA. Electronic address: johanng@med.umich.edu – sequence: 22 givenname: Stephan surname: Weidinger fullname: Weidinger, Stephan organization: Department of Dermatology and Allergy, University Hospital Schleswig-Holstein, Kiel, Germany
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Copyright	Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.
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PublicationTitle	Journal of investigative dermatology
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Snippet	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...
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SubjectTerms	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
Title	Atopic Dermatitis Is an IL-13-Dominant Disease with Greater Molecular Heterogeneity Compared to Psoriasis
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