Mice with epidermal filaggrin deficiency show increased immune reactivity to nickel. Academic Article uri icon

Overview

abstract

  • BACKGROUND: Nickel allergy and dermatitis have been associated with filaggrin gene mutations in epidemiological studies, but the mechanisms mediating these associations are unknown. OBJECTIVES: To investigate whether filaggrin-deficient flaky tail (ft/ft) mice show increased immune reactivity to nickel and elucidate the mechanisms mediating this. METHODS: The immune responses to nickel, 2,4-dinitrofluorobenzene (DNFB), cinnamal and p-phenylenediamine were assessed in ft/ft and wild-type (WT) mice. The amounts of nickel in the skin of ft/ft and WT mice were determined 20 hours after nickel exposure. The effect of blocking either the interleukin (IL)-17A pathway or the IL-1 pathway on the response to nickel in ft/ft mice was evaluated. RESULTS: Increased responsiveness to nickel, DNFB and cinnamal was observed in ft/ft mice as compared with controls. A reduced amount of nickel was found in the skin of ft/ft mice as compared with WT mice, suggesting increased nickel absorption by the skin of ft/ft mice. Blocking either the IL-17A pathway or the IL-1 pathway reduced nickel responsiveness in ft/ft mice. CONCLUSIONS: These findings suggest that the increased nickel responsiveness associated with epidermal filaggrin deficiency is mediated by a combination of increased nickel penetration and the steady-state inflammation found in the skin of filaggrin-deficient mice.

publication date

  • November 13, 2018

Research

keywords

  • Dermatitis, Atopic
  • Intermediate Filament Proteins
  • Nickel
  • Skin

Identity

Scopus Document Identifier

  • 85056420201

Digital Object Identifier (DOI)

  • 10.1111/cod.13153

PubMed ID

  • 30426511

Additional Document Info

volume

  • 80

issue

  • 3