TNF blockade induces a dysregulated type I interferon response without autoimmunity in paradoxical psoriasis.

Détails

ID Serval
serval:BIB_EF655037E4F5
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
TNF blockade induces a dysregulated type I interferon response without autoimmunity in paradoxical psoriasis.
Périodique
Nature communications
Auteur(s)
Conrad C., Di Domizio J., Mylonas A., Belkhodja C., Demaria O., Navarini A.A., Lapointe A.K., French L.E., Vernez M., Gilliet M.
ISSN
2041-1723 (Electronic)
ISSN-L
2041-1723
Statut éditorial
Publié
Date de publication
02/01/2018
Peer-reviewed
Oui
Volume
9
Numéro
1
Pages
25
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Résumé
Although anti-tumor necrosis factor (TNF) agents are highly effective in the treatment of psoriasis, 2-5% of treated patients develop psoriasis-like skin lesions called paradoxical psoriasis. The pathogenesis of this side effect and its distinction from classical psoriasis remain unknown. Here we show that skin lesions from patients with paradoxical psoriasis are characterized by a selective overexpression of type I interferons, dermal accumulation of plasmacytoid dendritic cells (pDC), and reduced T-cell numbers, when compared to classical psoriasis. Anti-TNF treatment prolongs type I interferon production by pDCs through inhibition of their maturation. The resulting type I interferon overexpression is responsible for the skin phenotype of paradoxical psoriasis, which, unlike classical psoriasis, is independent of T cells. These findings indicate that paradoxical psoriasis represents an ongoing overactive innate inflammatory process, driven by pDC-derived type I interferon that does not lead to T-cell autoimmunity.

Mots-clé
Adalimumab/adverse effects, Adalimumab/immunology, Adalimumab/therapeutic use, Adolescent, Adult, Aged, Animals, Antibodies, Monoclonal/adverse effects, Antibodies, Monoclonal/immunology, Antibodies, Monoclonal/therapeutic use, Autoimmunity/drug effects, Autoimmunity/immunology, Cells, Cultured, Crohn Disease/drug therapy, Crohn Disease/immunology, Crohn Disease/metabolism, Cytokines/genetics, Cytokines/immunology, Cytokines/metabolism, Dendritic Cells/drug effects, Dendritic Cells/immunology, Dendritic Cells/metabolism, Female, Humans, Infliximab/adverse effects, Infliximab/immunology, Infliximab/therapeutic use, Interferon Type I/genetics, Interferon Type I/immunology, Interferon Type I/metabolism, Male, Mice, Inbred BALB C, Middle Aged, Psoriasis/chemically induced, Psoriasis/immunology, T-Lymphocytes/drug effects, T-Lymphocytes/immunology, T-Lymphocytes/metabolism, Tumor Necrosis Factor-alpha/antagonists & inhibitors, Tumor Necrosis Factor-alpha/immunology, Tumor Necrosis Factor-alpha/metabolism, Young Adult
Pubmed
Web of science
Création de la notice
16/01/2018 16:22
Dernière modification de la notice
27/09/2018 13:25
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