IL-17 is produced by nickel-specific T lymphocytes and regulates ICAM-1 expression and chemokine production in human keratinocytes: synergistic or antagonist effects with IFN-gamma and TNF-alpha.
IL-17 is a novel T cell-derived cytokine that can regulate the functions of a variety of cell types. In this study, we investigated whether hapten-specific T cells isolated from patients with allergic contact dermatitis (ACD) to nickel produce IL-17 and the effects of IL-17 alone or in combination with IFN-gamma or TNF-alpha on the immune activation of keratinocytes. Skin affected with ACD to nickel and skin-derived, nickel-specific CD4+ T cell lines expressed IFN-gamma, TNF-alpha, and IL-17 mRNAs. Four of seven nickel-specific CD4+ T cell clones positive for the skin-homing receptor, cutaneous lymphocyte-associated Ag, were shown to corelease IL-17, IFN-gamma, and TNF-alpha. In contrast, two nickel-specific CD8+ T cell clones failed to synthesize IL-17. Normal human keratinocytes were found to express constitutively the IL-17 receptor gene. IL-17 specifically and dose-dependently augmented IFN-gamma-induced ICAM-1 expression on keratinocytes at both the mRNA and the protein level, whereas HLA-DR, MHC class I, and CD40 levels were not modulated by IL-17. On the other hand, IL-17 alone did not affect ICAM-1 or enhance TNF-alpha-induced ICAM-1. In addition, IL-17, both directly and in synergism with IFN-gamma and/or TNF-alpha, stimulated synthesis and release of IL-8 by keratinocytes. In contrast, IFN-gamma- and TNF-alpha-induced production of RANTES was markedly inhibited by IL-17, and the synthesis of macrophage chemotactic protein 1 was not changed. Taken together, the results suggest that IL-17 is an important player of T cell-mediated skin immune responses, with synergistic or antagonist effects on IFN-gamma- and TNF-alpha-stimulated keratinocyte activation.
Albanesi
C
C
Laboratory of Immunology, Istituto Dermopatico dell'Immacolata, IRCCS, Rome, Italy.
Cavani
A
A
Girolomoni
G
G
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002460:Cell Line; D018946:Chemokine CCL5 / Q000037:antagonists & inhibitors; D018925:Chemokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D002999:Clone Cells; D004357:Drug Synergism; D018984:Epitopes, T-Lymphocyte / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism / Q000502:physiology*; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000502:physiology*; D020381:Interleukin-17 / Q000096:biosynthesis* / Q000378:metabolism / Q000502:physiology; D016209:Interleukin-8 / Q000096:biosynthesis; D015603:Keratinocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D009532:Nickel / Q000276:immunology*; D018123:Receptors, Interleukin / Q000096:biosynthesis; D053722:Receptors, Interleukin-17; D011994:Recombinant Proteins / Q000096:biosynthesis; D012867:Skin / Q000166:cytology / Q000276:immunology; D012995:Solubility; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000502:physiology*
D000276:Adjuvants, Immunologic; D018946:Chemokine CCL5; D018925:Chemokines; D018984:Epitopes, T-Lymphocyte; C109985:IL17RA protein, human; D020381:Interleukin-17; D016209:Interleukin-8; D018123:Receptors, Interleukin; D053722:Receptors, Interleukin-17; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D009532:Nickel; D007371:Interferon-gamma