IL-23 and T(H)17-mediated inflammation in human allergic contact dermatitis

Jeppe Madura Larsen, Charlotte Menné Bonefeld, Steen Seier Poulsen, Carsten Geisler, Lone Skov

    Publikation: Bidrag til tidsskriftTidsskriftsartikelForskningpeer review

    Abstract

    BACKGROUND: IL-17-producing T(H) (T(H)17) cells are key mediators of chronic inflammation in mice. Recent studies have implicated T(H)17-mediated inflammation in the pathogenesis of human autoimmune diseases; however, the involvement of T(H)17 cells in allergic disorders remains largely elusive.

    OBJECTIVE: To investigate T(H)17-mediated inflammation in human beings with allergic contact dermatitis; in particular, the innate response of keratinocytes to contact allergen, the induction of allergen-specific T(H)17 cells, and the presence of T(H)17-related effector cells in inflamed skin.

    METHODS: Human keratinocytes were stimulated with nickel in vitro followed by measurements of IL-23 and IL-12 production by quantitative PCR and ELISA. Allergen-specific memory T cells from the blood of individuals with nickel allergy and healthy controls were identified and characterized by using a short-term ex vivo assay. Nickel patch test lesions and normal skin were analyzed for the expression of T(H)17-related cells and molecules by using immunohistochemistry.

    RESULTS: Keratinocytes were found to produce IL-23, but no detectable IL-12, in a response to nickel stimulation. Memory T cells isolated from peripheral blood of individuals with nickel allergy, but not healthy controls, contained T(H)17 and T(H)1 cells proliferating in response to nickel-pulsed DCs. Inflamed skin of nickel-challenged allergic individuals contained infiltrating neutrophils and cells expressing IL-17, IL-22, CCR6, and IL-22R.

    CONCLUSION: Our results demonstrate the involvement of T(H)17-mediated immunopathology in human allergic contact dermatitis, including both innate and adaptive immune responses to contact allergens.

    OriginalsprogEngelsk
    TidsskriftJournal of Allergy and Clinical Immunology
    Vol/bind123
    Udgave nummer2
    Sider (fra-til)486-92
    Antal sider7
    ISSN0091-6749
    DOI
    StatusUdgivet - feb. 2009

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