IL-23 and T(H)17-mediated inflammation in human allergic contact dermatitis.
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.
Larsen
Jeppe Madura
JM
Section of Experimental Immunology, Department of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
Bonefeld
Charlotte Menné
CM
Poulsen
Steen Seier
SS
Geisler
Carsten
C
Skov
Lone
L
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
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