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.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Contact Dermatitis |
| Sider (fra-til) | 139-148 |
| ISSN | 0105-1873 |
| DOI | |
| Status | Udgivet - mar. 2019 |