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

Conrad, Curdin and Di Domizio, Jeremy and Mylonas, Alessio and Belkhodja, Cyrine and Demaria, Olivier and Navarini, Alexander A. and Lapointe, Anne-Karine and French, Lars E. and Vernez, Maxime and Gilliet, Michel. (2018) TNF blockade induces a dysregulated type I interferon response without autoimmunity in paradoxical psoriasis. Nature Communications, 9 (1). p. 25.

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Official URL: https://edoc.unibas.ch/72809/

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Abstract

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.
Faculties and Departments:03 Faculty of Medicine > Bereich Spezialf├Ącher (Klinik) > Dermatologie USB > Dermatologie (Navarini)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Spezialf├Ącher (Klinik) > Dermatologie USB > Dermatologie (Navarini)
UniBasel Contributors:Navarini, Alexander
Item Type:Article, refereed
Article Subtype:Research Article
ISSN:2041-1723
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:05 Apr 2020 13:33
Deposited On:05 Apr 2020 13:33

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