title: IL-17 amplifies human contact hypersensitivity by licensing hapten nonspecific Th1 cells to kill autologous keratinocytes.
abstract: Th17 is a newly identified lineage of effector T cells involved in autoimmunity and immune responses to pathogens. We demonstrate in this study the pathogenic role of IL-17-producing CD4(+) T lymphocytes in allergic contact dermatitis (ACD) to skin-applied chemicals. IL-17(+) T cells infiltrate ACD reactions and predominantly distribute at the site of heavy spongiosis. Skin IL-17(+) T cells were functionally and phenotypically heterogeneous: although pure Th17 prevailed in ACD skin, hapten responsiveness was restricted to Th1/IL-17 (IFN-gamma(+)IL-17(+)) and Th0/IL-17 (IFN-gamma(+)IL-17(+)IL-4(+)) fractions, and to lesser extent Th2/IL-17 cells. In the IFN-gamma-dominated ACD environment, IL-17-releasing T cells affect immune function of keratinocytes by promoting CXCL8, IL-6, and HBD-2 production. In addition, compared with Th1, supernatants from Th1/IL-17 T cells were much more efficient in inducing ICAM-1 expression on keratinocytes and keratinocyte-T cell adhesiveness in vitro. As a consequence, exposure to combined IFN-gamma and IL-17 rendered keratinocytes susceptible to ICAM-1-dependent Ag nonspecific T cell killing. Thus, IL-17 efficiently amplifies the allergic reaction by rendering virtually all of the T lymphocytes recruited at the site of skin inflammation capable to directly contribute to tissue damage.
authors.affiliation: Laboratory of Experimental Immunology, Istituto Dermopatico dell'Immacolata-Istituto di Ricovero e Cura a Carattere Scientifico, Via dei Monti di Creta 104, 00167 Rome, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Pennino
authors.forename: Kilian
authors.initials: K
authors.lastname: Eyerich
authors.forename: Claudia
authors.initials: C
authors.lastname: Scarponi
authors.forename: Teresa
authors.initials: T
authors.lastname: Carbone
authors.forename: Stefanie
authors.initials: S
authors.lastname: Eyerich
authors.forename: Francesca
authors.initials: F
authors.lastname: Nasorri
authors.forename: Simone
authors.initials: S
authors.lastname: Garcovich
authors.forename: Claudia
authors.initials: C
authors.lastname: Traidl-Hoffmann
authors.forename: Cristina
authors.initials: C
authors.lastname: Albanesi
authors.forename: Andrea
authors.initials: A
authors.lastname: Cavani
mesh_terms: D016475:3T3 Cells; D000818:Animals; D017209:Apoptosis / Q000276:immunology; D002450:Cell Communication / Q000276:immunology; D016923:Cell Death / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism; D002999:Clone Cells; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D017449:Dermatitis, Allergic Contact / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D006241:Haptens / Q000276:immunology*; D006801:Humans; D018836:Inflammation Mediators / Q000502:physiology; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology; D020381:Interleukin-17 / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D015603:Keratinocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D009532:Nickel / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
chemical_list: D018925:Chemokines; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D006241:Haptens; D018836:Inflammation Mediators; D020381:Interleukin-17; D018799:Intercellular Adhesion Molecule-1; D009532:Nickel