Flightless I alters the inflammatory response and autoantibody profile in an OVA-induced atopic dermatitis skin-like disease

Zlatko Kopecki, Natalie E. Stevens, Heng T. Chong, Gink N. Yang, Allison J. Cowin

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Atopic dermatitis (AD) is a chronic pruritic inflammatory skin disease characterized by excessive inflammation and disrupted skin barrier function. Although the etiology of AD is not completely understood, clinical and basic studies suggest increasing involvement of autoantibodies against intracellular proteins. An actin remodeling protein, Flightless I (Flii), has been shown to promote development of inflammatory mediated skin conditions and impairment of skin barrier development and function. Here, we sought to determine the effect of altering Flii expression on the development of AD and its contribution to autoimmune aspects of inflammatory skin conditions. Ovalbumin (OVA)-induced AD skin-like disease was induced in Flii heterozygous (Flii+/-), wild-type (Flii+/+), and Flii transgenic (FliiTg/Tg) mice by epicutaneous exposure to OVA for 3 weeks; each week was separated by 2-week resting period. Reduced Flii expression resulted in decreased disease severity and tissue inflammation as determined by histology, lymphocytic, and mast cell infiltrate and increased anti-inflammatory IL-10 cytokine levels and a marked IFN-γ Th1 response. In contrast, Flii over-expression lead to a Th2 skewed response characterized by increased pro-inflammatory TNF-α cytokine production, Th2 chemokine levels, and Th2 cell numbers. Sera from OVA-induced AD skin-like disease Flii+/- mice showed a decreased level of autoreactivity while sera from FliiTg/Tg mice counterparts showed an altered autoantibody profile with strong nuclear localization favoring development of a more severe disease. These findings demonstrate autoimmune responses in this model of OVA-induced AD-like skin disease and suggest that Flii is a novel target, whose manipulation could be a potential approach for the treatment of patients with AD.

Original languageEnglish
Article number1833
JournalFrontiers in Immunology
Volume9
Issue numberAUG
DOIs
Publication statusPublished - 10 Aug 2018
Externally publishedYes

Keywords

  • Atopic dermatitis
  • Autoantibody
  • Flightless I
  • Inflammation
  • Skin barrier

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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