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PLoS One. 2014 Jul 10;9(7):e101937. doi: 10.1371/journal.pone.0101937. eCollection 2014.

Inhibition of keratinocyte differentiation by the synergistic effect of IL-17A, IL-22, IL-1α, TNFα and oncostatin M.

Author information

1
Laboratoire Inflammation Tissus Epithéliaux et Cytokines, Equipe Accueil 4331, Université de Poitiers, Poitiers, France.
2
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.
3
BIOalternatives, Gençay, France.
4
Service de Dermatologie, Centre Hospitalier Universitaire de Poitiers, Poitiers, France.
5
Service de Chirurgie Plastique, Centre Hospitalier Universitaire de Poitiers, Poitiers, France.
6
Laboratoire Inflammation Tissus Epithéliaux et Cytokines, Equipe Accueil 4331, Université de Poitiers, Poitiers, France; BIOalternatives, Gençay, France.

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.

PMID:
25010647
PMCID:
PMC4092099
DOI:
10.1371/journal.pone.0101937
[Indexed for MEDLINE]
Free PMC Article

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