title: IL-1β induces thymic stromal lymphopoietin and an atopic dermatitis-like phenotype in reconstructed healthy human epidermis.
abstract: Atopic dermatitis (AD) is a common skin inflammatory disease characterized by the production of thymic stromal lymphopoietin (TSLP) and marked TH2 polarization. Recent studies suggest that IL-1β contributes to the development of AD skin inflammation. Here, we have investigated the impact of IL-1β signalling on the epidermal homeostasis of both healthy subjects and AD patients [with functional filaggrin (FLG) alleles], with particular attention to TSLP production and keratinocyte differentiation. In healthy reconstructed human epidermis (RHE), IL-1β promoted (i) robust secretion of TSLP in an NF-κB-dependent manner and (ii) a significant decrease in the expression of filaggrin and other proteins of the epidermal differentiation complex. These effects were prevented by treatment of RHE with the anti-IL-1β mAb canakinumab and by the IL-1 receptor antagonist anakinra. Interestingly, RHE generated from AD donors behaved like that of healthy individuals and showed comparable responses to IL-1β signals. Collectively, our results suggest that IL-1β may be an early key mediator for the acquisition of an AD phenotype through induction of TSLP and alteration of the epidermal homeostasis. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
authors.affiliation: CIRI, International Center for Infectiology Research, Université de Lyon, Lyon, France.|Inserm, U1111, Lyon, France.|Ecole Normale Supérieure de Lyon, Lyon, France.|Université Lyon 1, Centre International de Recherche en Infectiologie, Lyon, France.|CNRS, UMR5308, Lyon, France.|Allergology & Clinical Immunology, CH Lyon-Sud, Pierre-Benite, France.|In vitro Pharmacology, Department R&D, Pierre Fabre Dermo-Cosmétique, Toulouse, France.
authors.forename: Marine
authors.initials: M
authors.lastname: Bernard
authors.affiliation: In vitro Pharmacology, Department R&D, Pierre Fabre Dermo-Cosmétique, Toulouse, France.
authors.forename: Cédric
authors.initials: C
authors.lastname: Carrasco
authors.affiliation: CIRI, International Center for Infectiology Research, Université de Lyon, Lyon, France.|Inserm, U1111, Lyon, France.|Ecole Normale Supérieure de Lyon, Lyon, France.|Université Lyon 1, Centre International de Recherche en Infectiologie, Lyon, France.|CNRS, UMR5308, Lyon, France.
authors.forename: Léo
authors.initials: L
authors.lastname: Laoubi
authors.affiliation: In vitro Pharmacology, Department R&D, Pierre Fabre Dermo-Cosmétique, Toulouse, France.
authors.forename: Béatrice
authors.initials: B
authors.lastname: Guiraud
authors.affiliation: CIRI, International Center for Infectiology Research, Université de Lyon, Lyon, France.|Inserm, U1111, Lyon, France.|Ecole Normale Supérieure de Lyon, Lyon, France.|Université Lyon 1, Centre International de Recherche en Infectiologie, Lyon, France.|CNRS, UMR5308, Lyon, France.|Allergology & Clinical Immunology, CH Lyon-Sud, Pierre-Benite, France.
authors.forename: Aurore
authors.initials: A
authors.lastname: Rozières
authors.affiliation: Allergology & Clinical Immunology, CH Lyon-Sud, Pierre-Benite, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Goujon
authors.affiliation: In vitro Pharmacology, Department R&D, Pierre Fabre Dermo-Cosmétique, Toulouse, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Duplan
authors.affiliation: In vitro Pharmacology, Department R&D, Pierre Fabre Dermo-Cosmétique, Toulouse, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Bessou-Touya
authors.affiliation: CIRI, International Center for Infectiology Research, Université de Lyon, Lyon, France.|Inserm, U1111, Lyon, France.|Ecole Normale Supérieure de Lyon, Lyon, France.|Université Lyon 1, Centre International de Recherche en Infectiologie, Lyon, France.|CNRS, UMR5308, Lyon, France.|Allergology & Clinical Immunology, CH Lyon-Sud, Pierre-Benite, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Nicolas
authors.affiliation: CIRI, International Center for Infectiology Research, Université de Lyon, Lyon, France.|Inserm, U1111, Lyon, France.|Ecole Normale Supérieure de Lyon, Lyon, France.|Université Lyon 1, Centre International de Recherche en Infectiologie, Lyon, France.|CNRS, UMR5308, Lyon, France.
authors.forename: Marc
authors.identifier: 0000-0002-0181-8862
authors.initials: M
authors.lastname: Vocanson
authors.affiliation: In vitro Pharmacology, Department R&D, Pierre Fabre Dermo-Cosmétique, Toulouse, France.
authors.forename: Marie-Florence
authors.identifier: 0000-0002-3342-2184
authors.initials: MF
authors.lastname: Galliano
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D002454:Cell Differentiation; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004817:Epidermis / Q000378:metabolism / Q000473:pathology; D005260:Female; D000091344:Filaggrin Proteins; D006706:Homeostasis; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000627:therapeutic use; D053583:Interleukin-1beta / Q000235:genetics* / Q000378:metabolism; D007381:Intermediate Filament Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D055815:Young Adult; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D016207:Cytokines; C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D053590:Interleukin 1 Receptor Antagonist Protein; D053583:Interleukin-1beta; D007381:Intermediate Filament Proteins; D016328:NF-kappa B; C541220:canakinumab; D000094632:Thymic Stromal Lymphopoietin
keywords: IL-1β; TSLP; atopic dermatitis; filaggrin; reconstructed human epidermis