title: IL-23 and T(H)17-mediated inflammation in human allergic contact dermatitis.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Section of Experimental Immunology, Department of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jeppe Madura
authors.initials: JM
authors.lastname: Larsen
authors.forename: Charlotte Menné
authors.initials: CM
authors.lastname: Bonefeld
authors.forename: Steen Seier
authors.initials: SS
authors.lastname: Poulsen
authors.forename: Carsten
authors.initials: C
authors.lastname: Geisler
authors.forename: Lone
authors.initials: L
authors.lastname: Skov
mesh_terms: D000485:Allergens / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D017449:Dermatitis, Allergic Contact / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism; D018664:Interleukin-12 / Q000276:immunology / Q000378:metabolism; D020381:Interleukin-17 / Q000276:immunology* / Q000378:metabolism; D053759:Interleukin-23 / Q000096:biosynthesis / Q000276:immunology* / Q000494:pharmacology; D007378:Interleukins / Q000276:immunology / Q000378:metabolism; D015603:Keratinocytes / Q000276:immunology* / Q000378:metabolism; D009532:Nickel / Q000276:immunology; D054399:Receptors, CCR6 / Q000276:immunology / Q000378:metabolism; D018123:Receptors, Interleukin / Q000276:immunology / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D000097043:Interleukin-22
chemical_list: D000485:Allergens; D018664:Interleukin-12; D020381:Interleukin-17; D053759:Interleukin-23; D007378:Interleukins; D009532:Nickel; D054399:Receptors, CCR6; D018123:Receptors, Interleukin; D000097043:Interleukin-22; C106311:CCR6 protein, human; C415369:interleukin-22 receptor