Major differences between human atopic dermatitis and murine models, as determined by using global transcriptomic profiling

David A. Ewald; Shinji Noda; Margeaux Oliva; Thomas Litman; Saeko Nakajima; Xuan Li; Hui Xu; Christopher T. Workman; Peter Scheipers; Naila Svitacheva; Tord Labuda; James G. Krueger; Mayte Suárez-Fariñas; Kenji Kabashima; Emma Guttman-Yassky

doi:10.1016/j.jaci.2016.08.029

Major differences between human atopic dermatitis and murine models, as determined by using global transcriptomic profiling

David A. Ewald, Shinji Noda, Margeaux Oliva, Thomas Litman, Saeko Nakajima, Xuan Li, Hui Xu, Christopher T. Workman, Peter Scheipers, Naila Svitacheva, Tord Labuda, James G. Krueger, Mayte Suárez-Fariñas, Kenji Kabashima, Emma Guttman-Yassky^*

^*Corresponding author af dette arbejde

63 Citationer (Scopus)

Abstract

Background Atopic dermatitis (AD) is caused by a complex interplay between immune and barrier abnormalities. Murine models of AD are essential for preclinical assessments of new treatments. Although many models have been used to simulate AD, their transcriptomic profiles are not fully understood, and a comparison of these models with the human AD transcriptomic fingerprint is lacking. Objective We sought to evaluate the transcriptomic profiles of 6 common murine models and determine how they relate to human AD skin. Methods Transcriptomic profiling was performed by using microarrays and quantitative RT-PCR on biopsy specimens from NC/Nga, flaky tail, Flg-mutated, ovalbumin-challenged, oxazolone-challenged, and IL-23–injected mice. Gene expression data of patients with AD, psoriasis, and contact dermatitis were obtained from previous patient cohorts. Criteria of a fold change of 2 or greater and a false discovery rate of 0.05 or less were used for gene arrays. Results IL-23–injected, NC/Nga, and oxazolone-challenged mice show the largest homology with our human meta-analysis–derived AD transcriptome (37%, 18%, 17%, respectively). Similar to human AD, robust T_H1, T_H2, and also T_H17 activation are seen in IL-23–injected and NC/Nga mice, with similar but weaker inflammation in ovalbumin-challenged mice. Oxazolone-challenged mice show a T_H1-centered reaction, and flaky tail mice demonstrate a strong T_H17 polarization. Flg-mutated mice display filaggrin downregulation without significant inflammation. Conclusion No single murine model fully captures all aspects of the AD profile; instead, each model reflects different immune or barrier disease aspects. Overall, among the 6 murine models, IL-23–injected mice best simulate human AD; still, the translational focus of the investigation should determine which model is most applicable.

Originalsprog	Engelsk
Tidsskrift	Journal of Allergy and Clinical Immunology
Vol/bind	139
Udgave nummer	2
Sider (fra-til)	562-571
Antal sider	10
ISSN	0091-6749
DOI	https://doi.org/10.1016/j.jaci.2016.08.029
Status	Udgivet - 2017

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10.1016/j.jaci.2016.08.029

Major differences between human atopic dermatitis and murine models as determined by global genomic profilingForlagets udgivne version, 1,23 MB

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Ewald, D. A., Noda, S., Oliva, M., Litman, T., Nakajima, S., Li, X., Xu, H., Workman, C. T., Scheipers, P., Svitacheva, N., Labuda, T., Krueger, J. G., Suárez-Fariñas, M., Kabashima, K., & Guttman-Yassky, E. (2017). Major differences between human atopic dermatitis and murine models, as determined by using global transcriptomic profiling. Journal of Allergy and Clinical Immunology, 139(2), 562-571. https://doi.org/10.1016/j.jaci.2016.08.029

Ewald, DA, Noda, S, Oliva, M, Litman, T, Nakajima, S, Li, X, Xu, H, Workman, CT, Scheipers, P, Svitacheva, N, Labuda, T, Krueger, JG, Suárez-Fariñas, M, Kabashima, K & Guttman-Yassky, E 2017, 'Major differences between human atopic dermatitis and murine models, as determined by using global transcriptomic profiling', Journal of Allergy and Clinical Immunology, bind 139, nr. 2, s. 562-571. https://doi.org/10.1016/j.jaci.2016.08.029

@article{550eb6754b844f7fbd2c478fec3ddf8e,

title = "Major differences between human atopic dermatitis and murine models, as determined by using global transcriptomic profiling",

abstract = "Background Atopic dermatitis (AD) is caused by a complex interplay between immune and barrier abnormalities. Murine models of AD are essential for preclinical assessments of new treatments. Although many models have been used to simulate AD, their transcriptomic profiles are not fully understood, and a comparison of these models with the human AD transcriptomic fingerprint is lacking. Objective We sought to evaluate the transcriptomic profiles of 6 common murine models and determine how they relate to human AD skin. Methods Transcriptomic profiling was performed by using microarrays and quantitative RT-PCR on biopsy specimens from NC/Nga, flaky tail, Flg-mutated, ovalbumin-challenged, oxazolone-challenged, and IL-23–injected mice. Gene expression data of patients with AD, psoriasis, and contact dermatitis were obtained from previous patient cohorts. Criteria of a fold change of 2 or greater and a false discovery rate of 0.05 or less were used for gene arrays. Results IL-23–injected, NC/Nga, and oxazolone-challenged mice show the largest homology with our human meta-analysis–derived AD transcriptome (37%, 18%, 17%, respectively). Similar to human AD, robust TH1, TH2, and also TH17 activation are seen in IL-23–injected and NC/Nga mice, with similar but weaker inflammation in ovalbumin-challenged mice. Oxazolone-challenged mice show a TH1-centered reaction, and flaky tail mice demonstrate a strong TH17 polarization. Flg-mutated mice display filaggrin downregulation without significant inflammation. Conclusion No single murine model fully captures all aspects of the AD profile; instead, each model reflects different immune or barrier disease aspects. Overall, among the 6 murine models, IL-23–injected mice best simulate human AD; still, the translational focus of the investigation should determine which model is most applicable.",

keywords = "Atopic dermatitis, contact dermatitis, filaggrin, IL-2, mouse model, NC/Nga, ovalbumin, oxazolone, psoriasis, T1, T17, T2",

author = "Ewald, {David A.} and Shinji Noda and Margeaux Oliva and Thomas Litman and Saeko Nakajima and Xuan Li and Hui Xu and Workman, {Christopher T.} and Peter Scheipers and Naila Svitacheva and Tord Labuda and Krueger, {James G.} and Mayte Su{\'a}rez-Fari{\~n}as and Kenji Kabashima and Emma Guttman-Yassky",

note = "The International Eczema Council selected this article as one of Top Ten articles on Atopic Dermatitis of 2016",

year = "2017",

doi = "10.1016/j.jaci.2016.08.029",

language = "English",

volume = "139",

pages = "562--571",

journal = "Journal of Allergy and Clinical Immunology",

issn = "0091-6749",

publisher = "Mosby Inc.",

number = "2",

}

TY - JOUR

T1 - Major differences between human atopic dermatitis and murine models, as determined by using global transcriptomic profiling

AU - Ewald, David A.

AU - Noda, Shinji

AU - Oliva, Margeaux

AU - Litman, Thomas

AU - Nakajima, Saeko

AU - Li, Xuan

AU - Xu, Hui

AU - Workman, Christopher T.

AU - Scheipers, Peter

AU - Svitacheva, Naila

AU - Labuda, Tord

AU - Krueger, James G.

AU - Suárez-Fariñas, Mayte

AU - Kabashima, Kenji

AU - Guttman-Yassky, Emma

N1 - The International Eczema Council selected this article as one of Top Ten articles on Atopic Dermatitis of 2016

PY - 2017

Y1 - 2017

N2 - Background Atopic dermatitis (AD) is caused by a complex interplay between immune and barrier abnormalities. Murine models of AD are essential for preclinical assessments of new treatments. Although many models have been used to simulate AD, their transcriptomic profiles are not fully understood, and a comparison of these models with the human AD transcriptomic fingerprint is lacking. Objective We sought to evaluate the transcriptomic profiles of 6 common murine models and determine how they relate to human AD skin. Methods Transcriptomic profiling was performed by using microarrays and quantitative RT-PCR on biopsy specimens from NC/Nga, flaky tail, Flg-mutated, ovalbumin-challenged, oxazolone-challenged, and IL-23–injected mice. Gene expression data of patients with AD, psoriasis, and contact dermatitis were obtained from previous patient cohorts. Criteria of a fold change of 2 or greater and a false discovery rate of 0.05 or less were used for gene arrays. Results IL-23–injected, NC/Nga, and oxazolone-challenged mice show the largest homology with our human meta-analysis–derived AD transcriptome (37%, 18%, 17%, respectively). Similar to human AD, robust TH1, TH2, and also TH17 activation are seen in IL-23–injected and NC/Nga mice, with similar but weaker inflammation in ovalbumin-challenged mice. Oxazolone-challenged mice show a TH1-centered reaction, and flaky tail mice demonstrate a strong TH17 polarization. Flg-mutated mice display filaggrin downregulation without significant inflammation. Conclusion No single murine model fully captures all aspects of the AD profile; instead, each model reflects different immune or barrier disease aspects. Overall, among the 6 murine models, IL-23–injected mice best simulate human AD; still, the translational focus of the investigation should determine which model is most applicable.

AB - Background Atopic dermatitis (AD) is caused by a complex interplay between immune and barrier abnormalities. Murine models of AD are essential for preclinical assessments of new treatments. Although many models have been used to simulate AD, their transcriptomic profiles are not fully understood, and a comparison of these models with the human AD transcriptomic fingerprint is lacking. Objective We sought to evaluate the transcriptomic profiles of 6 common murine models and determine how they relate to human AD skin. Methods Transcriptomic profiling was performed by using microarrays and quantitative RT-PCR on biopsy specimens from NC/Nga, flaky tail, Flg-mutated, ovalbumin-challenged, oxazolone-challenged, and IL-23–injected mice. Gene expression data of patients with AD, psoriasis, and contact dermatitis were obtained from previous patient cohorts. Criteria of a fold change of 2 or greater and a false discovery rate of 0.05 or less were used for gene arrays. Results IL-23–injected, NC/Nga, and oxazolone-challenged mice show the largest homology with our human meta-analysis–derived AD transcriptome (37%, 18%, 17%, respectively). Similar to human AD, robust TH1, TH2, and also TH17 activation are seen in IL-23–injected and NC/Nga mice, with similar but weaker inflammation in ovalbumin-challenged mice. Oxazolone-challenged mice show a TH1-centered reaction, and flaky tail mice demonstrate a strong TH17 polarization. Flg-mutated mice display filaggrin downregulation without significant inflammation. Conclusion No single murine model fully captures all aspects of the AD profile; instead, each model reflects different immune or barrier disease aspects. Overall, among the 6 murine models, IL-23–injected mice best simulate human AD; still, the translational focus of the investigation should determine which model is most applicable.

KW - Atopic dermatitis

KW - contact dermatitis

KW - filaggrin

KW - IL-2

KW - mouse model

KW - NC/Nga

KW - ovalbumin

KW - oxazolone

KW - psoriasis

KW - T1

KW - T17

KW - T2

U2 - 10.1016/j.jaci.2016.08.029

DO - 10.1016/j.jaci.2016.08.029

M3 - Journal article

C2 - 27702671

AN - SCOPUS:85006287975

SN - 0091-6749

VL - 139

SP - 562

EP - 571

JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

IS - 2

ER -

Major differences between human atopic dermatitis and murine models, as determined by using global transcriptomic profiling

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