IL-6 regulates neutrophil microabscess formation in IL-17A-driven psoriasiform lesions

J Invest Dermatol. 2014 Mar;134(3):728-735. doi: 10.1038/jid.2013.404. Epub 2013 Sep 25.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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

Substances

  • Il17a protein, mouse
  • Interleukin-17
  • Interleukin-6
  • Receptors, Interleukin-6
  • interleukin-6, mouse