title: IL-17 induces an expanded range of downstream genes in reconstituted human epidermis model.
abstract: BACKGROUND
  IL-17 is the defining cytokine of the Th17, Tc17, and γδ T cell populations that plays a critical role in mediating inflammation and autoimmunity. Psoriasis vulgaris is an inflammatory skin disease mediated by Th1 and Th17 cytokines with relevant contributions of IFN-γ, TNF-α, and IL-17. Despite the pivotal role IL-17 plays in psoriasis, and in contrast to the other key mediators involved in the psoriasis cytokine cascade that are capable of inducing broad effects on keratinocytes, IL-17 was demonstrated to regulate the expression of a limited number of genes in monolayer keratinocytes cultured in vitro.
  
  
  RESULTS
  Given the clinical efficacy of anti-IL-17 agents is associated with an impressive reduction in a large set of inflammatory genes, we sought a full-thickness skin model that more closely resemble in vivo epidermal architecture. Using a reconstructed human epidermis (RHE), IL-17 was able to upregulate 419 gene probes and downregulate 216 gene probes. As possible explanation for the increased gene induction in the RHE model is that C/CAAT-enhancer-binding proteins (C/EBP) -β, the transcription factor regulating IL-17-responsive genes, is expressed preferentially in differentiated keratinocytes.
  
  
  CONCLUSIONS
  The genes identified in IL-17-treated RHE are likely relevant to the IL-17 effects in psoriasis, since ixekizumab (anti-IL-17A agent) strongly suppressed the "RHE" genes in psoriasis patients treated in vivo with this IL-17 antagonist.
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York City, New York, United States of America ; Center for Clinical and Translational Science, The Rockefeller University, New York City, New York, United States of America ; Department of Dermatology, University of Rome "Tor Vergata", Rome, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Chiricozzi
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York City, New York, United States of America ; Center for Clinical and Translational Science, The Rockefeller University, New York City, New York, United States of America.
authors.forename: Kristine E
authors.initials: KE
authors.lastname: Nograles
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York City, New York, United States of America.
authors.forename: Leanne M
authors.initials: LM
authors.lastname: Johnson-Huang
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York City, New York, United States of America.
authors.forename: Judilyn
authors.initials: J
authors.lastname: Fuentes-Duculan
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York City, New York, United States of America.
authors.forename: Irma
authors.initials: I
authors.lastname: Cardinale
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York City, New York, United States of America.
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Bonifacio
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York City, New York, United States of America.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Gulati
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York City, New York, United States of America.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mitsui
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York City, New York, United States of America ; Center for Clinical and Translational Science, The Rockefeller University, New York City, New York, United States of America ; Department of Dermatology, Mount Sinai School of Medicine, New York City, New York, United States of America.
authors.forename: Emma
authors.initials: E
authors.lastname: Guttman-Yassky
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York City, New York, United States of America ; Center for Clinical and Translational Science, The Rockefeller University, New York City, New York, United States of America.
authors.forename: Mayte
authors.initials: M
authors.lastname: Suárez-Fariñas
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York City, New York, United States of America ; Center for Clinical and Translational Science, The Rockefeller University, New York City, New York, United States of America.
authors.forename: James G
authors.initials: JG
authors.lastname: Krueger
mesh_terms: D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics* / Q000378:metabolism; D000078404:Epidermal Cells; D004817:Epidermis / Q000187:drug effects* / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D020381:Interleukin-17 / Q000494:pharmacology*; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D054834:Lipocalins / Q000235:genetics / Q000378:metabolism; D046509:Tissue Culture Techniques; D023822:Tissue Engineering; D023083:beta-Defensins / Q000235:genetics / Q000378:metabolism
chemical_list: D022782:CCAAT-Enhancer-Binding Protein-beta; C545012:CEBPB protein, human; C106641:DEFB4A protein, human; D020381:Interleukin-17; D054834:Lipocalins; D023083:beta-Defensins