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IL-6 Regulates Neutrophil Microabscess Formation in IL-17A-Driven Psoriasiform Lesions

by Münzel, Thomas , Nikolaev, Alexei , Klebow, Sabrina , Brylla, Elke , Kurschus, Florian C. , Bechmann, Ingo , Piotrowski, Carolin , Wörtge, Simone , von Stebut, Esther , Croxford, Andrew L. , Schüler, Rebecca , Waisman, Ari , Reissig, Sonja , Thomas Wunderlich, F. , Karbach, Susanne , Scheller, Jürgen , Yogev, Nir , Rose-John, Stefan

in Abscess - drug therapy / Abscess - immunology / Abscess - pathology / Animals / Disease Models, Animal / Epidermis - immunology / Epidermis - metabolism / Epidermis - pathology / Gene Expression - immunology / Granulocytes - immunology / Granulocytes - pathology / Interleukin-17 - genetics / Interleukin-17 - immunology / Interleukin-17 - metabolism / Interleukin-6 - immunology / Interleukin-6 - metabolism / Interleukin-6 - pharmacology / Macrophages - immunology / Macrophages - pathology / Mice / Mice, Knockout / Neutrophils - immunology / Neutrophils - metabolism / Psoriasis - drug therapy / Psoriasis - immunology / Psoriasis - pathology / Receptors, Interleukin-6 - genetics / Receptors, Interleukin-6 - immunology / Signal Transduction - drug effects / Signal Transduction - immunology / T-Lymphocytes - immunology / T-Lymphocytes - pathology

2014

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IL-6 Regulates Neutrophil Microabscess Formation in IL-17A-Driven Psoriasiform Lesions

2014

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IL-6 Regulates Neutrophil Microabscess Formation in IL-17A-Driven Psoriasiform Lesions

2014

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Journal Article

IL-6 Regulates Neutrophil Microabscess Formation in IL-17A-Driven Psoriasiform Lesions

Münzel, Thomas,

Nikolaev, Alexei,

Klebow, Sabrina,

Brylla, Elke,

Kurschus, Florian C.,

Bechmann, Ingo,

Piotrowski, Carolin,

Wörtge, Simone,

von Stebut, Esther,

Croxford, Andrew L.,

Schüler, Rebecca,

Waisman, Ari,

Reissig, Sonja,

Thomas Wunderlich, F.,

Karbach, Susanne,

Scheller, Jürgen,

Yogev, Nir,

Rose-John, Stefan

2014

Overview

The lack of a generally accepted animal model for human psoriasis has hindered progress with respect to understanding the pathogenesis of the disease. Here we present a model in which transgenic IL-17A expression is targeted to the skin in mice, achievable after crossing our IL-17Aind allele to the K14-Cre strain. K14-IL-17Aind/+ mice invariably develop an overt skin inflammation bearing many hallmark characteristics of human psoriasis including dermal infiltration of effector T cells, formation of neutrophil microabscesses, and hyperkeratosis. IL-17A expression in the skin results in upregulated granulopoiesis and migration of IL-6R-expressing neutrophils into the skin. Neutralization of IL-6 signaling efficiently reduces the observed pathogenesis in skin of IL-17A-overexpressing mice, with marked reductions in epidermal neutrophil abscess formation and epidermal thickening. Thus, IL-6 functions downstream of IL-17A to exacerbate neutrophil microabscess development in psoriasiform lesions.

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Publisher

Elsevier Inc,Elsevier Limited

Subject

Abscess - drug therapy

/ Abscess - immunology

/ Abscess - pathology

/ Animals

/ Disease Models, Animal

/ Epidermis - immunology

/ Epidermis - metabolism