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Mice with epidermal filaggrin deficiency show increased immune reactivity to nickel

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  • Trine H Petersen
  • Mia H Jee
  • Anne-Sofie Ø Gadsbøll
  • Jonas D Schmidt
  • Jens J Sloth
  • Gregory F Sonnenberg
  • Carsten Geisler
  • Jacob P Thyssen
  • Charlotte M Bonefeld
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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.

Original languageEnglish
JournalContact Dermatitis
Volume80
Issue number3
Pages (from-to)139-148
Number of pages10
ISSN0105-1873
DOIs
Publication statusPublished - Mar 2019

ID: 56510135