Mice with epidermal filaggrin deficiency show increased immune reactivity to nickel

TY - JOUR

T1 - Mice with epidermal filaggrin deficiency show increased immune reactivity to nickel

AU - Petersen, Trine H.

AU - Jee, Mia H.

AU - Gadsbøll, Anne Sofie Ø.

AU - Schmidt, Jonas D.

AU - Sloth, Jens J.

AU - Sonnenberg, Gregory F.

AU - Geisler, Carsten

AU - Thyssen, Jacob P.

AU - Bonefeld, Charlotte M.

PY - 2019/3

Y1 - 2019/3

N2 - 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.

AB - 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.

KW - allergic contact dermatitis

KW - filaggrin

KW - IL-17A

KW - IL-1β

KW - nickel

U2 - 10.1111/cod.13153

DO - 10.1111/cod.13153

M3 - Journal article

C2 - 30426511

AN - SCOPUS:85056420201

SN - 0105-1873

SP - 139

EP - 148

JO - Contact Dermatitis

JF - Contact Dermatitis

ER -