IL‐1β induces thymic stromal lymphopoietin and an atopic dermatitis‐like phenotype in reconstructed healthy human epidermis

Atopic dermatitis (AD) is a common skin inflammatory disease characterized by the production of thymic stromal lymphopoietin (TSLP) and marked TH2 polarization. Recent studies suggest that IL‐1β contributes to the development of AD skin inflammation. Here, we have investigated the impact of IL‐1β si...

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Veröffentlicht in:The Journal of Pathology 2017-06, Vol.242 (2), p.234-245
Hauptverfasser: Bernard, Marine, Carrasco, Cédric, Laoubi, Léo, Guiraud, Béatrice, Rozières, Aurore, Goujon, Catherine, Duplan, Hélène, Bessou‐Touya, Sandrine, Nicolas, Jean‐François, Vocanson, Marc, Galliano, Marie‐Florence
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container_title The Journal of Pathology
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creator Bernard, Marine
Carrasco, Cédric
Laoubi, Léo
Guiraud, Béatrice
Rozières, Aurore
Goujon, Catherine
Duplan, Hélène
Bessou‐Touya, Sandrine
Nicolas, Jean‐François
Vocanson, Marc
Galliano, Marie‐Florence
description Atopic dermatitis (AD) is a common skin inflammatory disease characterized by the production of thymic stromal lymphopoietin (TSLP) and marked TH2 polarization. Recent studies suggest that IL‐1β contributes to the development of AD skin inflammation. Here, we have investigated the impact of IL‐1β signalling on the epidermal homeostasis of both healthy subjects and AD patients [with functional filaggrin (FLG) alleles], with particular attention to TSLP production and keratinocyte differentiation. In healthy reconstructed human epidermis (RHE), IL‐1β promoted (i) robust secretion of TSLP in an NF‐κB‐dependent manner and (ii) a significant decrease in the expression of filaggrin and other proteins of the epidermal differentiation complex. These effects were prevented by treatment of RHE with the anti‐IL‐1β mAb canakinumab and by the IL‐1 receptor antagonist anakinra. Interestingly, RHE generated from AD donors behaved like that of healthy individuals and showed comparable responses to IL‐1β signals. Collectively, our results suggest that IL‐1β may be an early key mediator for the acquisition of an AD phenotype through induction of TSLP and alteration of the epidermal homeostasis. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
doi_str_mv 10.1002/path.4887
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Recent studies suggest that IL‐1β contributes to the development of AD skin inflammation. Here, we have investigated the impact of IL‐1β signalling on the epidermal homeostasis of both healthy subjects and AD patients [with functional filaggrin (FLG) alleles], with particular attention to TSLP production and keratinocyte differentiation. In healthy reconstructed human epidermis (RHE), IL‐1β promoted (i) robust secretion of TSLP in an NF‐κB‐dependent manner and (ii) a significant decrease in the expression of filaggrin and other proteins of the epidermal differentiation complex. These effects were prevented by treatment of RHE with the anti‐IL‐1β mAb canakinumab and by the IL‐1 receptor antagonist anakinra. Interestingly, RHE generated from AD donors behaved like that of healthy individuals and showed comparable responses to IL‐1β signals. Collectively, our results suggest that IL‐1β may be an early key mediator for the acquisition of an AD phenotype through induction of TSLP and alteration of the epidermal homeostasis. Copyright © 2017 Pathological Society of Great Britain and Ireland. 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subjects Adult
Antibodies, Monoclonal - therapeutic use
atopic dermatitis
Bacteriology
Cell Differentiation
Cytokines - genetics
Cytokines - secretion
Dermatitis, Atopic - drug therapy
Dermatitis, Atopic - genetics
Dermatitis, Atopic - metabolism
Dermatitis, Atopic - pathology
Epidermis - metabolism
Epidermis - pathology
Female
filaggrin
Homeostasis
Humans
IL‐1β
Immunology
Interleukin 1 Receptor Antagonist Protein - therapeutic use
Interleukin-1beta - genetics
Interleukin-1beta - metabolism
Intermediate Filament Proteins - genetics
Intermediate Filament Proteins - metabolism
Life Sciences
Male
Microbiology and Parasitology
Middle Aged
NF-kappa B - genetics
NF-kappa B - metabolism
Phenotype
reconstructed human epidermis
TSLP
Virology
Young Adult
title IL‐1β induces thymic stromal lymphopoietin and an atopic dermatitis‐like phenotype in reconstructed healthy human epidermis
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