Major differences between human atopic dermatitis and murine models, as determined by using global transcriptomic profiling
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Major differences between human atopic dermatitis and murine models, as determined by using global transcriptomic profiling. / Ewald, David A.; Noda, Shinji; Oliva, Margeaux; Litman, Thomas; Nakajima, Saeko; Li, Xuan; Xu, Hui; Workman, Christopher T.; Scheipers, Peter; Svitacheva, Naila; Labuda, Tord; Krueger, James G.; Suárez-Fariñas, Mayte; Kabashima, Kenji; Guttman-Yassky, Emma.
In: Journal of Allergy and Clinical Immunology, Vol. 139, No. 2, 2017, p. 562-571.Research output: Contribution to journal › Journal article › Research › peer-review
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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
VL - 139
SP - 562
EP - 571
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
SN - 0091-6749
IS - 2
ER -
ID: 184382394