3 years ago

Interleukin-17A-induced production of acute serum amyloid A by keratinocytes contributes to psoriasis pathogenesis

Mathilde Pohin, Pierre Levillain, Laure Favot, Magalie Camus, Amandine Buffière-Morgado, François-Xavier Bernard, Hans Yssel, Camille Paquier, Jiad Mcheik, Jean-François Jégou, Elodie Couderc, Franck Morel, Jean-Claude Lecron, Vincent Huguier, Gérard Guillet, Charles Bodet, Corinne Lacombe, Martine Garcia

by Elodie Couderc, Franck Morel, Pierre Levillain, Amandine Buffière-Morgado, Magalie Camus, Camille Paquier, Charles Bodet, Jean-François Jégou, Mathilde Pohin, Laure Favot, Martine Garcia, Vincent Huguier, Jiad Mcheik, Corinne Lacombe, Hans Yssel, Gérard Guillet, François-Xavier Bernard, Jean-Claude Lecron

Background

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.

Objectives

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.

Methods

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.

Results

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.

Conclusion

Keratinocytes could contribute to psoriasis pathogenesis via A-SAA production, maintaining a cutaneous inflammatory environment, activating innate immunity and Th17 lymphocyte recruitment.

Publisher URL: http://journals.plos.org/plosone/article

DOI: 10.1371/journal.pone.0181486

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