title: Differential Features between Chronic Skin Inflammatory Diseases Revealed in Skin-Humanized Psoriasis and Atopic Dermatitis Mouse Models.
abstract: Psoriasis and atopic dermatitis are chronic and relapsing inflammatory diseases of the skin affecting a large number of patients worldwide. Psoriasis is characterized by a T helper type 1 and/or T helper type 17 immunological response, whereas acute atopic dermatitis lesions exhibit T helper type 2-dominant inflammation. Current single gene and signaling pathways-based models of inflammatory skin diseases are incomplete. Previous work allowed us to model psoriasis in skin-humanized mice through proper combinations of inflammatory cell components and disruption of barrier function. Herein, we describe and characterize an animal model for atopic dermatitis using similar bioengineered-based approaches, by intradermal injection of human T helper type 2 lymphocytes in regenerated human skin after partial removal of stratum corneum. In this work, we have extensively compared this model with the previous and an improved version of the psoriasis model, in which T helper type 1 and/or T helper type 17 lymphocytes replace exogenous cytokines. Comparative expression analyses revealed marked differences in specific epidermal proliferation and differentiation markers and immune-related molecules, including antimicrobial peptides. Likewise, the composition of the dermal inflammatory infiltrate presented important differences. The availability of accurate and reliable animal models for these diseases will contribute to the understanding of the pathogenesis and provide valuable tools for drug development and testing.
authors.affiliation: Epithelial Biomedicine Division, Basic Research Department, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT), Madrid, Spain; Centre for Biomedical Research on Rare Diseases (CIBERER), ISCIII, Valencia, Spain; Fundación Jiménez Díaz Healthcare Research Institute (IIS FJD), Madrid, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Carretero
authors.affiliation: Centre for Biomedical Research on Rare Diseases (CIBERER), ISCIII, Valencia, Spain; Fundación Jiménez Díaz Healthcare Research Institute (IIS FJD), Madrid, Spain; Department of Bioengineering, Carlos III University (UC3M), Madrid, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Guerrero-Aspizua
authors.affiliation: Epithelial Biomedicine Division, Basic Research Department, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT), Madrid, Spain; Centre for Biomedical Research on Rare Diseases (CIBERER), ISCIII, Valencia, Spain; Fundación Jiménez Díaz Healthcare Research Institute (IIS FJD), Madrid, Spain.
authors.forename: Nuria
authors.initials: N
authors.lastname: Illera
authors.affiliation: Epithelial Biomedicine Division, Basic Research Department, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT), Madrid, Spain; Centre for Biomedical Research on Rare Diseases (CIBERER), ISCIII, Valencia, Spain; Fundación Jiménez Díaz Healthcare Research Institute (IIS FJD), Madrid, Spain.
authors.forename: Victoria
authors.initials: V
authors.lastname: Galvez
authors.affiliation: Molecular Oncology Unit, Basic Research Department, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT), Madrid, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Navarro
authors.affiliation: Computational Genomics Department, Centro de Investigación Príncipe Felipe (CIPF), Valencia, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: García-García
authors.affiliation: Centre for Biomedical Research on Rare Diseases (CIBERER), ISCIII, Valencia, Spain; Computational Genomics Department, Centro de Investigación Príncipe Felipe (CIPF), Valencia, Spain; Functional Genomics Node, Instituto Nacional de Bioinformática (INB), CIPF, Valencia, Spain.
authors.forename: Joaquin
authors.initials: J
authors.lastname: Dopazo
authors.affiliation: Epithelial Biomedicine Division, Basic Research Department, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT), Madrid, Spain; Department of Bioengineering, Carlos III University (UC3M), Madrid, Spain.
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Jorcano
authors.affiliation: Epithelial Biomedicine Division, Basic Research Department, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT), Madrid, Spain; Centre for Biomedical Research on Rare Diseases (CIBERER), ISCIII, Valencia, Spain; Fundación Jiménez Díaz Healthcare Research Institute (IIS FJD), Madrid, Spain. Electronic address: fernando.larcher@ciemat.es.
authors.forename: Fernando
authors.initials: F
authors.lastname: Larcher
authors.affiliation: Epithelial Biomedicine Division, Basic Research Department, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT), Madrid, Spain; Centre for Biomedical Research on Rare Diseases (CIBERER), ISCIII, Valencia, Spain; Fundación Jiménez Díaz Healthcare Research Institute (IIS FJD), Madrid, Spain; Department of Bioengineering, Carlos III University (UC3M), Madrid, Spain. Electronic address: marcela.delrio@uc3m.es.
authors.forename: Marcela
authors.initials: M
authors.lastname: del Rio
mesh_terms: D000818:Animals; D001707:Biopsy, Needle; D049109:Cell Proliferation; D002908:Chronic Disease; D016207:Cytokines / Q000276:immunology / Q000378:metabolism*; D003876:Dermatitis, Atopic / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology; D004195:Disease Models, Animal; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D011565:Psoriasis / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology; D011897:Random Allocation; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D016207:Cytokines; D000094632:Thymic Stromal Lymphopoietin