title: Major differences between human atopic dermatitis and murine models, as determined by using global transcriptomic profiling.
abstract: 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.
  
  
  
  We sought to evaluate the transcriptomic profiles of 6 common murine models and determine how they relate to human AD skin.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Laboratory for Investigative Dermatology, Rockefeller University, New York, NY; Exploratory Biology, LEO Pharma A/S, Ballerup, Denmark; Regulatory Genomics, Integrative Systems Biology, Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Kgs. Lyngby, Denmark.
authors.forename: David A
authors.initials: DA
authors.lastname: Ewald
authors.affiliation: Laboratory for Investigative Dermatology, Rockefeller University, New York, NY.
authors.forename: Shinji
authors.initials: S
authors.lastname: Noda
authors.affiliation: Department of Dermatology and the Laboratory for Inflammatory Skin Diseases, Icahn School of Medicine at Mount Sinai, New York, NY.
authors.forename: Margeaux
authors.initials: M
authors.lastname: Oliva
authors.affiliation: Exploratory Biology, LEO Pharma A/S, Ballerup, Denmark; Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Thomas
authors.initials: T
authors.lastname: Litman
authors.affiliation: Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Saeko
authors.initials: S
authors.lastname: Nakajima
authors.affiliation: Laboratory for Investigative Dermatology, Rockefeller University, New York, NY.
authors.forename: Xuan
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Dermatology and the Laboratory for Inflammatory Skin Diseases, Icahn School of Medicine at Mount Sinai, New York, NY.
authors.forename: Hui
authors.initials: H
authors.lastname: Xu
authors.affiliation: Regulatory Genomics, Integrative Systems Biology, Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Kgs. Lyngby, Denmark.
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Workman
authors.affiliation: Exploratory Biology, LEO Pharma A/S, Ballerup, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Scheipers
authors.affiliation: In Vivo Biology, LEO Pharma A/S, Ballerup, Denmark.
authors.forename: Naila
authors.initials: N
authors.lastname: Svitacheva
authors.affiliation: Translational Medicine, LEO Pharma A/S, Ballerup, Denmark.
authors.forename: Tord
authors.initials: T
authors.lastname: Labuda
authors.affiliation: Laboratory for Investigative Dermatology, Rockefeller University, New York, NY.
authors.forename: James G
authors.initials: JG
authors.lastname: Krueger
authors.affiliation: Laboratory for Investigative Dermatology, Rockefeller University, New York, NY; Department of Dermatology, the Departments of Population Health Science and Policy, and the Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY.
authors.forename: Mayte
authors.initials: M
authors.lastname: Suárez-Fariñas
authors.affiliation: Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan; Singapore Immunology Network (SIgN) and Institute of Medical Biology, Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore.
authors.forename: Kenji
authors.initials: K
authors.lastname: Kabashima
authors.affiliation: Laboratory for Investigative Dermatology, Rockefeller University, New York, NY; Department of Dermatology and the Laboratory for Inflammatory Skin Diseases, Icahn School of Medicine at Mount Sinai, New York, NY. Electronic address: Emma.Guttman@mountsinai.org.
authors.forename: Emma
authors.initials: E
authors.lastname: Guttman-Yassky
mesh_terms: D000328:Adult; D000368:Aged; D000485:Allergens / Q000276:immunology; D000818:Animals; D015331:Cohort Studies; D003876:Dermatitis, Atopic / Q000235:genetics*; D003877:Dermatitis, Contact / Q000235:genetics*; D004195:Disease Models, Animal; D005260:Female; D000091344:Filaggrin Proteins; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D053759:Interleukin-23 / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008875:Middle Aged; D010047:Ovalbumin / Q000276:immunology; D010081:Oxazolone; D011565:Psoriasis / Q000235:genetics*; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics; D012867:Skin / Q000276:immunology* / Q000473:pathology; D046888:Tissue Array Analysis; D055815:Young Adult
chemical_list: D000485:Allergens; C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D053759:Interleukin-23; D010081:Oxazolone; D010047:Ovalbumin; C496349:Fgfr1 protein, mouse; D051496:Receptor, Fibroblast Growth Factor, Type 1
keywords: Atopic dermatitis; IL-2; NC/Nga; T(H)1; T(H)17; T(H)2; contact dermatitis; filaggrin; mouse model; ovalbumin; oxazolone; psoriasis