title: Interleukin-17 is produced by both Th1 and Th2 lymphocytes, and modulates interferon-gamma- and interleukin-4-induced activation of human keratinocytes.
abstract: Interleukin-17 is a T-cell-derived cytokine, detected in skin affected by allergic contact dermatitis and psoriasis, which regulates keratinocyte expression of adhesion molecules and chemokines. In this study, we have analyzed whether interleukin-17 production segregates with a particular T helper (Th) cell subset, and have examined the capacity of interleukin-17 to modulate the activation of keratinocytes induced by Th1 and Th2 cytokines. A panel of 80 nickel-specific CD4+ T cell clones (36 Th0, 30 Th1, and 14 Th2) was isolated from peripheral blood or lesional skin of allergic contact dermatitis patients. Significant amounts (> 50 pg per ml) of interleukin-17 were released by about 50% of activated Th0, Th1, and Th2 cells. Interleukin-17 alone and in cooperation with interleukin-4, or to a lesser extent with interferon-gamma, decreased the interleukin-1 receptor antagonist to interleukin-1alpha ratio in the supernatants as well as in cell lysates from keratinocytes. In addition, interleukin-17 stimulated the release of growth-regulated oncogene-alpha, granulocyte-macrophage colony stimulating factor, and interleukin-6, with synergistic or additive effects when used together with interferon-gamma or interleukin-4. Interleukin-17 and interleukin-4 also increased stem cell factor release, a function that was inhibited by interferon-gamma. Moreover, interleukin-17 and interleukin-4 enhanced interferon-gamma-induced expression of intercellular adhesion molecule 1, but not CD40, on keratinocytes. The constitutive expression of interleukin-17 and interferon-gamma receptors on keratinocytes was not modulated by interleukin-17, interferon-gamma, or interleukin-4, whereas the interleukin-4 receptor was significantly downregulated by interferon-gamma. As a whole, the results indicate that interleukin-17 can participate relevantly in T-cell-mediated skin immune responses by amplifying both interferon-gamma- and interleukin-4-induced activation of keratinocytes.
authors.affiliation: Laboratory of Immunology, Istituto Dermopatico dell'Immacolata, IRCCS, Rome, Italy. c.albanesi@idi.it
authors.forename: C
authors.initials: C
authors.lastname: Albanesi
authors.forename: C
authors.initials: C
authors.lastname: Scarponi
authors.forename: A
authors.initials: A
authors.lastname: Cavani
authors.forename: M
authors.initials: M
authors.lastname: Federici
authors.forename: F
authors.initials: F
authors.lastname: Nasorri
authors.forename: G
authors.initials: G
authors.lastname: Girolomoni
mesh_terms: D054360:Chemokine CXCL1; D019743:Chemokines, CXC; D002630:Chemotactic Factors / Q000378:metabolism; D002999:Clone Cells; D017449:Dermatitis, Allergic Contact / Q000276:immunology; D000939:Epitopes; D006133:Growth Substances / Q000378:metabolism; D006801:Humans; D007111:Immunity, Cellular; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D036341:Intercellular Signaling Peptides and Proteins; D007371:Interferon-gamma / Q000494:pharmacology*; D020381:Interleukin-17 / Q000096:biosynthesis* / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D015603:Keratinocytes / Q000187:drug effects / Q000276:immunology* / Q000502:physiology*; D009532:Nickel / Q000276:immunology; D011565:Psoriasis / Q000276:immunology; D019089:Stem Cell Factor / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology; D018417:Th1 Cells / Q000166:cytology / Q000378:metabolism*; D018418:Th2 Cells / Q000166:cytology / Q000378:metabolism*
chemical_list: C475829:CXCL1 protein, human; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; D002630:Chemotactic Factors; D000939:Epitopes; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D020381:Interleukin-17; D019089:Stem Cell Factor; D018799:Intercellular Adhesion Molecule-1; D015847:Interleukin-4; D009532:Nickel; D007371:Interferon-gamma