Skin hepcidin initiates psoriasiform skin inflammation via Fe-driven hyperproliferation and neutrophil recruitment

Elise Abboud, Doha Chrayteh, Nadia Boussetta, Héloise Dalle, Mariangela Malerba, Ting-Di Wu, Morgane Gall, Olivier Reelfs, Charareh Pourzand, Mark Mellett, Florence Assan, Hervé Bachelez, Joël Poupon, Selim Aractingi, Sophie Vaulont, Pierre Sohier, Bénédicte Oules, Zoubida Karim and Carole Peyssonnaux ()
Additional contact information
Elise Abboud: Institut Cochin
Doha Chrayteh: Institut Cochin
Nadia Boussetta: Institut Cochin
Héloise Dalle: Institut Cochin
Mariangela Malerba: Institut Cochin
Ting-Di Wu: Multimodal Imaging Center
Morgane Gall: Institut Cochin
Olivier Reelfs: University of Bath
Charareh Pourzand: University of Bath
Mark Mellett: University of Zürich (UZH)
Florence Assan: Université Paris Cité
Hervé Bachelez: Université Paris Cité
Joël Poupon: AP-HP
Selim Aractingi: Institut Cochin
Sophie Vaulont: Institut Cochin
Pierre Sohier: Institut Cochin
Bénédicte Oules: Institut Cochin
Zoubida Karim: Université Paul Sabatier (UPS)
Carole Peyssonnaux: Institut Cochin

Nature Communications, 2024, vol. 15, issue 1, 1-14

Abstract: Abstract Psoriasis is a multifactorial, chronic inflammatory skin disease with unresolved questions on its primary events. Iron overload has been described in the epidermis of psoriasis patients, but its relevance remains unknown. We found that the key iron regulatory hormone hepcidin was highly expressed in the epidermis of psoriasis patients, especially the pustular variants resistant to treatments. In a murine model of acute skin inflammation, keratinocyte-derived hepcidin was required for iron retention in keratinocytes, leading to hyperproliferation of the epidermal layer and neutrophil recruitment, two main features of psoriatic skin lesions. Keratinocytes overexpressing hepcidin were sufficient to elicit these psoriasiform features in a transgenic mouse model. Furthermore, transcriptome analysis of these keratinocytes revealed canonical pathways found in human psoriasis, pointing to a causal role for hepcidin in the pathogenesis of the disease. Altogether, our data suggest that hepcidin could be an actionable target for skin psoriasis treatment, in addition to current therapeutics, or targeted as maintenance therapy during remission to prevent recurrence.

Date: 2024
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DOI: 10.1038/s41467-024-50993-8

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