Psoriasis is a common, inflammatory immune-mediated skin disease mainly presenting with plaques whose pathogenesis is based on the central role of interleukin (IL)-23/IL-17 axis. However, the mechanisms acting in papular lesions of early-phase psoriasis are not fully understood. The aim of this study was assessing the involvement of autoinflammation, a state of sterile inflammation mainly driven by IL-1 overproduction that has been recently hypothesised to act in early phase of disease. Lesional skin of 10 patients with recent onset, untreated psoriasis has been investigated for expression of IL-1β, IL-17, IL-23 and other cytokines involved in the disease in comparison with normal skin of 10 healthy controls using a protein array method. Immunohistochemical phenotyping of inflammatory infiltrate and co-localisation experiments with immunofluorescence confocal microscopy were conducted. IL-1β was significantly more expressed in psoriasis than in normal skin (p<0.0001). The chemokine IL-8 was also overexpressed in psoriasis (p=0.03) while IL-12, IL-17, IL-23, tumour necrosis factor-α and interferon-γ were only slightly more expressed in psoriasis than in normal skin, without reaching statistical significance. The inflammatory infiltrate consisted mainly of neutrophils with a relevant number of macrophages and dendritic cells and only scattered, predominantly T helper 1 lymphocytes. IL-1β co-localised mainly with CD66b, a neutrophil marker, suggesting that neutrophils were the major source of this cytokine. IL-1β overexpression in combination with low expression of cytokines that are predominant in late-phase plaque psoriasis may support the role of autoinflammation in early-phase disease, possibly paving the way to randomised trials with IL-1 antagonists.

Evidence for a role of autoinflammation in early-phase psoriasis / D. Fanoni, L. Venegoni, B. Vergani, S. Tavecchio, A. Cattaneo, B.E. Leone, E. Berti, A.V. Marzano. - In: CLINICAL AND EXPERIMENTAL IMMUNOLOGY. - ISSN 0009-9104. - 198:3(2019 Dec 01), pp. 283-291. [10.1111/cei.13370]

Evidence for a role of autoinflammation in early-phase psoriasis

D. Fanoni
Primo
;
L. Venegoni
Secondo
;
B. Vergani;S. Tavecchio;E. Berti
Penultimo
;
A.V. Marzano
Ultimo
2019

Abstract

Psoriasis is a common, inflammatory immune-mediated skin disease mainly presenting with plaques whose pathogenesis is based on the central role of interleukin (IL)-23/IL-17 axis. However, the mechanisms acting in papular lesions of early-phase psoriasis are not fully understood. The aim of this study was assessing the involvement of autoinflammation, a state of sterile inflammation mainly driven by IL-1 overproduction that has been recently hypothesised to act in early phase of disease. Lesional skin of 10 patients with recent onset, untreated psoriasis has been investigated for expression of IL-1β, IL-17, IL-23 and other cytokines involved in the disease in comparison with normal skin of 10 healthy controls using a protein array method. Immunohistochemical phenotyping of inflammatory infiltrate and co-localisation experiments with immunofluorescence confocal microscopy were conducted. IL-1β was significantly more expressed in psoriasis than in normal skin (p<0.0001). The chemokine IL-8 was also overexpressed in psoriasis (p=0.03) while IL-12, IL-17, IL-23, tumour necrosis factor-α and interferon-γ were only slightly more expressed in psoriasis than in normal skin, without reaching statistical significance. The inflammatory infiltrate consisted mainly of neutrophils with a relevant number of macrophages and dendritic cells and only scattered, predominantly T helper 1 lymphocytes. IL-1β co-localised mainly with CD66b, a neutrophil marker, suggesting that neutrophils were the major source of this cytokine. IL-1β overexpression in combination with low expression of cytokines that are predominant in late-phase plaque psoriasis may support the role of autoinflammation in early-phase disease, possibly paving the way to randomised trials with IL-1 antagonists.
autoinflammatory disease; cytokines; neutrophils; skin
Settore MED/35 - Malattie Cutanee e Veneree
11-set-2019
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/675683
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