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Contact Dermatitis. 2019 Mar;80(3):139-148. doi: 10.1111/cod.13153. Epub 2018 Nov 13.

Mice with epidermal filaggrin deficiency show increased immune reactivity to nickel.

Author information

1
Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
2
Department of Dermatology and Allergy, National Allergy Research Centre, Copenhagen University Hospital Gentofte, Hellerup, Denmark.
3
National Food Institute, Technical University of Denmark, Kongens Lyngby, Denmark.
4
Department of Medicine, Weill Cornell Medicine, New York, New York.

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.

KEYWORDS:

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

PMID:
30426511
DOI:
10.1111/cod.13153
[Indexed for MEDLINE]

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