2024-09-26 バース大学
<関連情報>
- https://www.bath.ac.uk/announcements/a-cure-for-psoriasis-could-a-faulty-iron-hormone-in-the-skin-be-the-key/
- https://www.nature.com/articles/s41467-024-50993-8
皮膚ヘプシジンは、鉄主導の過剰増殖と好中球の動員を介して乾癬様皮膚炎症を引き起こす 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 Le Gall,Olivier Reelfs,Charareh Pourzand,Mark Mellett,Florence Assan,Hervé Bachelez,Joël Poupon,Selim Aractingi,Sophie Vaulont,Pierre Sohier,Bénédicte Oules,Zoubida Karim &Carole Peyssonnaux
Nature Communications Published:07 August 2024
DOI:https://doi.org/10.1038/s41467-024-50993-8
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.
