Mice with epidermal filaggrin deficiency show increased immune reactivity to nickel

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.

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