Mice with epidermal filaggrin deficiency show increased immune reactivity to nickel

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

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Nickel allergy and dermatitis have been associated with filaggrin gene mutations in epidemiological studies, but the mechanisms mediating these associations are unknown. To investigate whether filaggrin-deficient flaky tail (ft/ft) mice show increased immune reactivity to nickel and elucidate the mechanisms mediating this. 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. 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. 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
ISSN0105-1873
DOIs
Publication statusPublished - 2019

Keywords

  • IL-17A
  • IL-1β
  • allergic contact dermatitis
  • filaggrin
  • nickel

Cite this

Petersen, T. H., Jee, M. H., Gadsbøll, A-S. Ø., Schmidt, J. D., Sloth, J. J., Sonnenberg, G. F., ... Bonefeld, C. M. (2019). Mice with epidermal filaggrin deficiency show increased immune reactivity to nickel. Contact Dermatitis, 80(3), 139-148. https://doi.org/10.1111/cod.13153