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

Autor: Abboud E; Université Paris Cité, CNRS, INSERM, Institut Cochin, Paris, France.; Laboratory of Excellence GR-Ex, Paris, France., Chrayteh D; Université Paris Cité, CNRS, INSERM, Institut Cochin, Paris, France.; Laboratory of Excellence GR-Ex, Paris, France., Boussetta N; Université Paris Cité, CNRS, INSERM, Institut Cochin, Paris, France.; Laboratory of Excellence GR-Ex, Paris, France., Dalle H; Université Paris Cité, CNRS, INSERM, Institut Cochin, Paris, France.; Laboratory of Excellence GR-Ex, Paris, France., Malerba M; Université Paris Cité, CNRS, INSERM, Institut Cochin, Paris, France.; Laboratory of Excellence GR-Ex, Paris, France., Wu TD; Institut Curie, PSL University, Université Paris-Saclay, CNRS UAR2016, Inserm US43, Multimodal Imaging Center, Orsay, France., Le Gall M; Proteom'IC facility, Université Paris Cité, CNRS, INSERM, Institut Cochin, Paris, France., Reelfs O; Department of Life Sciences, University of Bath, Bath, United Kingdom., Pourzand C; Department of Life Sciences, University of Bath, Bath, United Kingdom.; Medicines Development, Centre for Therapeutic Innovation, University of Bath, Bath, United Kingdom., Mellett M; Department of Dermatology, University Hospital Zürich (USZ), University of Zürich (UZH), Zürich, Switzerland., Assan F; Laboratory of Genetic Skin Diseases, INSERM U1163, Imagine Institute, Université Paris Cité, Paris, France., Bachelez H; Laboratory of Genetic Skin Diseases, INSERM U1163, Imagine Institute, Université Paris Cité, Paris, France.; Department of Dermatology, Hôpital Saint-Louis APHP, Université Paris Cité, Paris, France., Poupon J; Laboratoire de Toxicologie Biologique, Hôpital Lariboisière, Paris, France. Assistance Publique - Hôpitaux de Paris, AP-HP, Paris, France., Aractingi S; Université Paris Cité, CNRS, INSERM, Institut Cochin, Paris, France.; Service de Dermatologie, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Paris, France., Vaulont S; Université Paris Cité, CNRS, INSERM, Institut Cochin, Paris, France.; Laboratory of Excellence GR-Ex, Paris, France., Sohier P; Université Paris Cité, CNRS, INSERM, Institut Cochin, Paris, France.; Department of Pathology, Cochin Hospital, Assistance Publique - Hôpitaux de Paris, AP-HP. Centre-Université Paris Cité, Paris, France., Oules B; Université Paris Cité, CNRS, INSERM, Institut Cochin, Paris, France.; Service de Dermatologie, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Paris, France., Karim Z; Université de Toulouse, INSERM, CNRS, Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Paul Sabatier (UPS), Toulouse, France., Peyssonnaux C; Université Paris Cité, CNRS, INSERM, Institut Cochin, Paris, France. carole.peyssonnaux@inserm.fr.; Laboratory of Excellence GR-Ex, Paris, France. carole.peyssonnaux@inserm.fr.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Aug 07; Vol. 15 (1), pp. 6718. Date of Electronic Publication: 2024 Aug 07.
DOI: 10.1038/s41467-024-50993-8
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
Externí odkaz: