Mice with epidermal filaggrin deficiency show increased immune reactivity to nickel

Research output: Contribution to journalJournal article – Annual report year: 2019Researchpeer-review

DOI

  • Author: Petersen, Trine H

    University of Copenhagen

  • Author: Jee, Mia H

    University of Copenhagen

  • Author: Gadsbøll, Anne-Sofie Ø

    University of Copenhagen

  • Author: Schmidt, Jonas Damgard

    University of Copenhagen

  • Author: Sloth, Jens Jørgen

    Research group for Nano-Bio Science, National Food Institute, Technical University of Denmark, Kemitorvet, 2800, Kgs. Lyngby, Denmark

  • Author: Sonnenberg, Gregory F

    Weill Cornell Medical College

  • Author: Geisler, Carsten

    University of Copenhagen

  • Author: Thyssen, Jacob P.

    University of Copenhagen, Denmark

  • Author: Bonefeld, Charlotte M.

    University of Copenhagen

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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
CitationsWeb of Science® Times Cited: No match on DOI

    Research areas

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

ID: 160660457