Mice with epidermal filaggrin deficiency show increased immune reactivity to nickel
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Mice with epidermal filaggrin deficiency show increased immune reactivity to nickel. / Petersen, Trine H.; Jee, Mia H.; Gadsbøll, Anne Sofie Ø.; Schmidt, Jonas D.; Sloth, Jens J.; Sonnenberg, Gregory F.; Geisler, Carsten; Thyssen, Jacob P.; Bonefeld, Charlotte M.
In: Contact Dermatitis, 2019, p. 139-148.Research output: Contribution to journal › Journal article › Research › peer-review
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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
Y1 - 2019
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
SP - 139
EP - 148
JO - Contact Dermatitis
JF - Contact Dermatitis
SN - 0105-1873
ER -
ID: 210064753