Interleukin-17A-induced production of acute serum amyloid A by keratinocytes contributes to psoriasis pathogenesis
PLoS ONE, 12(7)
COUDERC E., MOREL F., LEVILLAIN P., BUFFIÈRE-MORGADO A., CAMUS M., PAQUIER C., BODET C., JÉGOU JF., POHIN M., FAVOT L., GARCIA M., HUGUIER V., MCHEIK J., LACOMBE C., YSSEL H., GUILLET G., BERNARD FX., LECRON JC. (2017)
Laboratoire Inflammation, Tissus Epithéliaux et Cytokines, UPRES EA4331, Pôle Biologie Santé , Université de Poitiers, France.
Service de Dermatologie, CHU de Poitiers, Poitiers, France.
Service d’Anatomopathologie, CHU de Poitiers, Poitiers, France.
Service de Chirurgie plastique, CHU de Poitiers, Poitiers, France.
Service de Chirurgie pédiatrique, CHU de Poitiers, Poitiers, France.
Service d’Immunologie et Inflammation, CHU de Poitiers, Poitiers, France.
Centre d’Immunologie et des Maladies Infectieuses, Inserm U1135, Hôpital Pitié-Salpêtrière, Paris, France.
Bioalternatives, Gençay, France.
Acute-serum Amyloid A (A-SAA), one of the major acute-phase proteins, is mainly produced in the liver but extra-hepatic synthesis involving the skin has been reported. Its expression is regulated by the transcription factors NF-κB, C/EBPβ, STAT3 activated by proinflammatory cytokines.
We investigated A-SAA synthesis by resting and cytokine-activated Normal Human Epidermal Keratinocytes (NHEK), and their inflammatory response to A-SAA stimulation. A-SAA expression was also studied in mouse skin and liver in a model mimicking psoriasis and in the skin and sera of psoriatic and atopic dermatitis (AD) patients.
NHEK were stimulated by A-SAA or the cytokines IL-1α, IL-17A, IL-22, OSM, TNF-α alone or in combination, previously reported to reproduce features of psoriasis. Murine skins were treated by imiquimod cream. Human skins and sera were obtained from patients with psoriasis and AD. A-SAA mRNA was quantified by RT qPCR. A-SAA proteins were dosed by ELISA or immunonephelemetry assay.
IL-1α, TNF-α and mainly IL-17A induced A-SAA expression by NHEK. A-SAA induced its own production and the synthesis of hBD2 and CCL20, both ligands for CCR6, a chemokine receptor involved in the trafficking of Th17 lymphocytes. A-SAA expression was increased in skins and livers from imiquimod-treated mice and in patient skins with psoriasis, but not significantly in those with AD. Correlations between A-SAA and psoriasis severity and duration were observed.
Keratinocytes could contribute to psoriasis pathogenesis via A-SAA production, maintaining a cutaneous inflammatory environment, activating innate immunity and Th17 lymphocyte recruitment.
© 2017 Couderc et al.
KEYWORDS: atopic dermatitis, antimicrobial peptide, Acute Serum Amyloid A, dendritic cell, Normal Human Epidermal Keratinocyte