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-γ and TNF-α

Cristina Albanesi, Andrea Cavani, Giampiero Girolomoni

Research output: Contribution to journalArticlepeer-review

Abstract

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-γ or TNF-α on the immune activation of keratinocytes. Skin affected with ACD to nickel and skin-derived, nickel-specific CD4+ T cell lines expressed IFN-γ, TNF-α, 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-γ, and TNF-α. 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-γ- 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-α- induced ICAM-1. In addition, IL-17, both directly and in synergism with IFN- γ and/or TNF-α, stimulated synthesis and release of IL-8 by keratinocytes. In contrast, IFN-γ- and TNF-α. 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-γ,- and TNFα-stimulated keratinocyte activation.

Original languageEnglish
Pages (from-to)494-502
Number of pages9
JournalJournal of Immunology
Volume162
Issue number1
Publication statusPublished - Jan 1 1999

ASJC Scopus subject areas

  • Immunology

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