Mice with epidermal filaggrin deficiency show increased immune reactivity to nickel

Trine H Petersen, Mia H Jee, Anne-Sofie Ø Gadsbøll, Jonas D Schmidt, Jens Jørgen Sloth, Gregory F Sonnenberg, Carsten Geisler, Jacob P Thyssen, Charlotte M Bonefeld*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Nickel allergy and dermatitis have been associated with filaggrin gene mutations in epidemiological studies, but the mechanisms mediating these associations are unknown. To investigate whether filaggrin-deficient flaky tail (ft/ft) mice show increased immune reactivity to nickel and elucidate the mechanisms mediating this. 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. 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. 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.
Original languageEnglish
JournalContact Dermatitis
Volume80
Issue number3
Pages (from-to)139-148
ISSN0105-1873
DOIs
Publication statusPublished - 2019

Keywords

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

Cite this

Petersen, T. H., Jee, M. H., Gadsbøll, A-S. Ø., Schmidt, J. D., Sloth, J. J., Sonnenberg, G. F., ... Bonefeld, C. M. (2019). Mice with epidermal filaggrin deficiency show increased immune reactivity to nickel. Contact Dermatitis, 80(3), 139-148. https://doi.org/10.1111/cod.13153
Petersen, Trine H ; Jee, Mia H ; Gadsbøll, Anne-Sofie Ø ; Schmidt, Jonas D ; Sloth, Jens Jørgen ; Sonnenberg, Gregory F ; Geisler, Carsten ; Thyssen, Jacob P ; Bonefeld, Charlotte M. / Mice with epidermal filaggrin deficiency show increased immune reactivity to nickel. In: Contact Dermatitis. 2019 ; Vol. 80, No. 3. pp. 139-148.
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abstract = "Nickel allergy and dermatitis have been associated with filaggrin gene mutations in epidemiological studies, but the mechanisms mediating these associations are unknown. To investigate whether filaggrin-deficient flaky tail (ft/ft) mice show increased immune reactivity to nickel and elucidate the mechanisms mediating this. 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. 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. 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",
author = "Petersen, {Trine H} and Jee, {Mia H} and Gadsb{\o}ll, {Anne-Sofie {\O}} and Schmidt, {Jonas D} and Sloth, {Jens J{\o}rgen} and Sonnenberg, {Gregory F} and Carsten Geisler and Thyssen, {Jacob P} and Bonefeld, {Charlotte M}",
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Petersen, TH, Jee, MH, Gadsbøll, A-SØ, Schmidt, JD, Sloth, JJ, Sonnenberg, GF, Geisler, C, Thyssen, JP & Bonefeld, CM 2019, 'Mice with epidermal filaggrin deficiency show increased immune reactivity to nickel', Contact Dermatitis, vol. 80, no. 3, pp. 139-148. https://doi.org/10.1111/cod.13153

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 Jørgen; Sonnenberg, Gregory F; Geisler, Carsten; Thyssen, Jacob P; Bonefeld, Charlotte M.

In: Contact Dermatitis, Vol. 80, No. 3, 2019, p. 139-148.

Research output: Contribution to journalJournal articleResearchpeer-review

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 Jørgen

AU - Sonnenberg, Gregory F

AU - Geisler, Carsten

AU - Thyssen, Jacob P

AU - Bonefeld, Charlotte M

PY - 2019

Y1 - 2019

N2 - Nickel allergy and dermatitis have been associated with filaggrin gene mutations in epidemiological studies, but the mechanisms mediating these associations are unknown. To investigate whether filaggrin-deficient flaky tail (ft/ft) mice show increased immune reactivity to nickel and elucidate the mechanisms mediating this. 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. 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. 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 - Nickel allergy and dermatitis have been associated with filaggrin gene mutations in epidemiological studies, but the mechanisms mediating these associations are unknown. To investigate whether filaggrin-deficient flaky tail (ft/ft) mice show increased immune reactivity to nickel and elucidate the mechanisms mediating this. 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. 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. 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 - IL-17A

KW - IL-1β

KW - allergic contact dermatitis

KW - filaggrin

KW - nickel

U2 - 10.1111/cod.13153

DO - 10.1111/cod.13153

M3 - Journal article

VL - 80

SP - 139

EP - 148

JO - Contact Dermatitis

JF - Contact Dermatitis

SN - 0105-1873

IS - 3

ER -