title: Dose-dependent effects of IL-17 on IL-13-induced airway inflammatory responses and airway hyperresponsiveness.
abstract: The Th2 cytokine IL-13 regulates several aspects of the asthmatic phenotype, including airway inflammation, airway hyperresponsiveness, and mucus production. The Th17 cytokine IL-17A is also implicated in asthma and has been shown to both positively and negatively regulate Th2-dependent responses in murine models of allergic airways disease. Our objective in this study was to better understand the role of IL-17 in airway inflammation by examining how IL-17 modifies IL-13-induced airway inflammatory responses. We treated BALB/c mice intranasally with IL-13 or IL-17 alone or in combination for 8 consecutive days, after which airway hyperresponsiveness, inflammatory cell influx into the lung, and lung chemokine/cytokine expression were assessed. As expected, IL-13 increased airway inflammation and airway hyperresponsiveness. IL-13 also increased numbers of IL-17-producing CD4(+) and γδ T cells. Treating mice with a combination of IL-13 and IL-17 reduced infiltration of IL-17(+) γδ T cells, but increased the number of infiltrating eosinophils. In contrast, coadministration of IL-13 with a higher dose of IL-17 decreased all IL-13-induced inflammatory responses, including infiltration of both IL-17(+)CD4(+) and γδ T cells. To examine the inhibitory activity of IL-17-expressing γδ T cells in this model, these cells were adoptively transferred into naive recipients. Consistent with an inhibitory role for γδ T cells, IL-13-induced infiltration of eosinophils, lymphocytes, and IL-17(+)CD4(+) T cells was diminished in recipients of the γδ T cells. Collectively, our data indicate that allergic airway inflammatory responses induced by IL-13 are modulated by both the quantity and the cellular source of IL-17.
authors.affiliation: Meakins-Christie Laboratories, McGill University, Montreal, Quebec H2X 2P2, Canada.
authors.forename: Margaret W
authors.initials: MW
authors.lastname: Kinyanjui
authors.forename: Jichuan
authors.initials: J
authors.lastname: Shan
authors.forename: Emily M
authors.initials: EM
authors.lastname: Nakada
authors.forename: Salman T
authors.initials: ST
authors.lastname: Qureshi
authors.forename: Elizabeth D
authors.initials: ED
authors.lastname: Fixman
mesh_terms: D000818:Animals; D016535:Bronchial Hyperreactivity / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D004306:Dose-Response Relationship, Immunologic; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D018793:Interleukin-13 / Q000494:pharmacology*; D020381:Interleukin-17 / Q000172:deficiency / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism
chemical_list: D018793:Interleukin-13; D020381:Interleukin-17; D016692:Receptors, Antigen, T-Cell, gamma-delta