IL-6 regulates neutrophil microabscess formation in IL-17A-driven psoriasiform lesions.
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-17A(ind) allele to the K14-Cre strain. K14-IL-17A(ind/+) 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.
Institute for Molecular Medicine, University Medical Center of the Johannes-Gutenberg University of Mainz, Mainz, Germany; Institute of Experimental Immunology, University of Zürich, Zürich, Switzerland.
Andrew L
AL
Croxford
Institute for Molecular Medicine, University Medical Center of the Johannes-Gutenberg University of Mainz, Mainz, Germany; Department of Medicine 2, University Medical Center of the Johannes-Gutenberg University of Mainz, Mainz, Germany.
Susanne
S
Karbach
Institute for Molecular Medicine, University Medical Center of the Johannes-Gutenberg University of Mainz, Mainz, Germany.
Florian C
FC
Kurschus
Institute for Molecular Medicine, University Medical Center of the Johannes-Gutenberg University of Mainz, Mainz, Germany.
Simone
S
Wörtge
Institute for Molecular Medicine, University Medical Center of the Johannes-Gutenberg University of Mainz, Mainz, Germany.
Alexei
A
Nikolaev
Institute for Molecular Medicine, University Medical Center of the Johannes-Gutenberg University of Mainz, Mainz, Germany.
Nir
N
Yogev
Institute for Molecular Medicine, University Medical Center of the Johannes-Gutenberg University of Mainz, Mainz, Germany.
Sabrina
S
Klebow
Institute for Molecular Medicine, University Medical Center of the Johannes-Gutenberg University of Mainz, Mainz, Germany.
Rebecca
R
Schüler
Institute for Molecular Medicine, University Medical Center of the Johannes-Gutenberg University of Mainz, Mainz, Germany.
Sonja
S
Reissig
Institute of Anatomy, University of Leipzig, Leipzig, Germany.
Carolin
C
Piotrowski
Institute of Anatomy, University of Leipzig, Leipzig, Germany.
Elke
E
Brylla
Institute of Anatomy, University of Leipzig, Leipzig, Germany.
Ingo
I
Bechmann
Department of Dermatology, University Medical Center of the Johannes-Gutenberg University of Mainz, Mainz, Germany.
Jürgen
J
Scheller
Institute for Biochemistry, Christian-Albrechts-University of Kiel, Kiel, Germany.
Stefan
S
Rose-John
Department of Mouse Genetics and Metabolism, Institute for Genetics, University of Cologne, Cologne, Germany.
F
F
Thomas Wunderlich
Department of Medicine 2, University Medical Center of the Johannes-Gutenberg University of Mainz, Mainz, Germany; Center for Thrombosis and Hemostasis, University Medical Center of the Johannes-Gutenberg University of Mainz, Mainz, Germany.
Thomas
T
Münzel
Department of Dermatology, University Medical Center of the Johannes-Gutenberg University of Mainz, Mainz, Germany.
Esther
E
von Stebut
Institute for Molecular Medicine, University Medical Center of the Johannes-Gutenberg University of Mainz, Mainz, Germany. Electronic address: waisman@uni-mainz.de.
Ari
A
Waisman
D000038:Abscess / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D000818:Animals; D004195:Disease Models, Animal; D004817:Epidermis / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression / Q000276:immunology; D006098:Granulocytes / Q000276:immunology / Q000473:pathology; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015850:Interleukin-6 / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D008264:Macrophages / Q000276:immunology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism; D011565:Psoriasis / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D019947:Receptors, Interleukin-6 / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology
C098680:Il17a protein, mouse; D020381:Interleukin-17; D015850:Interleukin-6; D019947:Receptors, Interleukin-6; C577686:interleukin-6, mouse