title: Inhibition of keratinocyte differentiation by the synergistic effect of IL-17A, IL-22, IL-1α, TNFα and oncostatin M.
abstract: Keratinocyte differentiation program leading to an organized epidermis plays a key role in maintaining the first line of defense of the skin. Epidermal integrity is regulated by a tight communication between keratinocytes and leucocytes, particularly under cytokine control. Imbalance of the cytokine network leads to inflammatory diseases such as psoriasis. Our attempt to model skin inflammation showed that the combination of IL-17A, IL-22, IL-1α, OSM and TNFα (Mix M5) synergistically increases chemokine and antimicrobial-peptide expression, recapitulating some features of psoriasis. Other characteristics of psoriasis are acanthosis and down-regulation of keratinocyte differentiation markers. Our aim was to characterize the specific roles of these cytokines on keratinocyte differentiation, and to compare with psoriatic lesion features. All cytokines decrease keratinocyte differentiation markers, but IL-22 and OSM were the most powerful, and the M5 strongly synergized the effects. In addition, IL-22 and OSM induced epidermal hyperplasia in vitro and M5 induced epidermal thickening and decreased differentiation marker expression in a mouse model, as observed in human psoriatic skin lesions. This study highlights the precise role of cytokines in the skin inflammatory response. IL-22 and OSM more specifically drive epidermal hyperplasia and differentiation loss while IL-1α, IL-17A and TNFα were more involved in the activation of innate immunity.
authors.affiliation: Laboratoire Inflammation Tissus Epithéliaux et Cytokines, Equipe Accueil 4331, Université de Poitiers, Poitiers, France.
authors.forename: Hanitriniaina
authors.initials: H
authors.lastname: Rabeony
authors.affiliation: Laboratoire Inflammation Tissus Epithéliaux et Cytokines, Equipe Accueil 4331, Université de Poitiers, Poitiers, France; Laboratoire Immunologie et Inflammation, Centre Hospitalier Universitaire de Poitiers, Poitiers, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Petit-Paris
authors.affiliation: BIOalternatives, Gençay, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Garnier
authors.affiliation: BIOalternatives, Gençay, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Barrault
authors.affiliation: BIOalternatives, Gençay, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Pedretti
authors.affiliation: Laboratoire Inflammation Tissus Epithéliaux et Cytokines, Equipe Accueil 4331, Université de Poitiers, Poitiers, France.
authors.forename: Karline
authors.initials: K
authors.lastname: Guilloteau
authors.affiliation: Laboratoire Inflammation Tissus Epithéliaux et Cytokines, Equipe Accueil 4331, Université de Poitiers, Poitiers, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Jegou
authors.affiliation: Service de Dermatologie, Centre Hospitalier Universitaire de Poitiers, Poitiers, France.
authors.forename: Gérard
authors.initials: G
authors.lastname: Guillet
authors.affiliation: Service de Chirurgie Plastique, Centre Hospitalier Universitaire de Poitiers, Poitiers, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Huguier
authors.affiliation: Laboratoire Inflammation Tissus Epithéliaux et Cytokines, Equipe Accueil 4331, Université de Poitiers, Poitiers, France; Laboratoire Immunologie et Inflammation, Centre Hospitalier Universitaire de Poitiers, Poitiers, France.
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Lecron
authors.affiliation: Laboratoire Inflammation Tissus Epithéliaux et Cytokines, Equipe Accueil 4331, Université de Poitiers, Poitiers, France; BIOalternatives, Gençay, France.
authors.forename: François-Xavier
authors.initials: FX
authors.lastname: Bernard
authors.affiliation: Laboratoire Inflammation Tissus Epithéliaux et Cytokines, Equipe Accueil 4331, Université de Poitiers, Poitiers, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Morel
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D016207:Cytokines / Q000494:pharmacology*; D000078404:Epidermal Cells; D006801:Humans; D018836:Inflammation Mediators / Q000494:pharmacology; D020381:Interleukin-17 / Q000494:pharmacology; D053582:Interleukin-1alpha / Q000494:pharmacology; D007378:Interleukins / Q000494:pharmacology; D015603:Keratinocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D053683:Oncostatin M / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D000097043:Interleukin-22
chemical_list: D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators; D020381:Interleukin-17; D053582:Interleukin-1alpha; D007378:Interleukins; D053683:Oncostatin M; D014409:Tumor Necrosis Factor-alpha; D000097043:Interleukin-22