IL-23 and T(H)17-mediated inflammation in human allergic contact dermatitis
Research output: Contribution to journal › Journal article › Research › peer-review
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.
Original language | English |
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Journal | Journal of Allergy and Clinical Immunology |
Volume | 123 |
Issue number | 2 |
Pages (from-to) | 486-92 |
Number of pages | 6 |
ISSN | 0091-6749 |
DOIs | |
Publication status | Published - 2009 |
Bibliographical note
Keywords: Allergens; Cell Proliferation; Cells, Cultured; Dermatitis, Allergic Contact; Humans; Inflammation; Interleukin-12; Interleukin-17; Interleukin-23; Interleukins; Keratinocytes; Nickel; Receptors, CCR6; Receptors, Interleukin; T-Lymphocytes, Helper-Inducer
ID: 14119328