title: An IL-17F/A heterodimer protein is produced by mouse Th17 cells and induces airway neutrophil recruitment.
abstract: IL-17A and IL-17F are related homodimeric proteins of the IL-17 family produced by Th17 cells. In this study, we show that mouse Th17 cells also produce an IL-17F/A heterodimeric protein. Whereas naive CD4(+) T cells differentiating toward the Th17 cell lineage expressed IL-17F/A in higher amounts than IL-17A/A homodimer and in lower amounts than IL-17F/F homodimer, differentiated Th17 cells expressed IL-17F/A in higher amounts than either homodimer. In vitro, IL-17F/A was more potent than IL-17F/F and less potent than IL-17A/A in regulating CXCL1 expression. Neutralization of IL-17F/A with an IL-17A-specific Ab, and not with an IL-17F-specific Ab, reduced the majority of IL-17F/A-induced CXCL1 expression. To study these cytokines in vivo, we established a Th17 cell adoptive transfer model characterized by increased neutrophilia in the airways. An IL-17A-specific Ab completely prevented Th17 cell-induced neutrophilia and CXCL5 expression, whereas Abs specific for IL-17F or IL-22, a cytokine also produced by Th17 cells, had no effects. Direct administration of mouse IL-17A/A or IL-17F/A, and not IL-17F/F or IL-22, into the airways significantly increased neutrophil and chemokine expression. Taken together, our data elucidate the regulation of IL-17F/A heterodimer expression by Th17 cells and demonstrate an in vivo function for this cytokine in airway neutrophilia.
authors.affiliation: Inflammation Technologies, Wyeth Research, Cambridge, MA 02140, USA.
authors.forename: Spencer C
authors.initials: SC
authors.lastname: Liang
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Long
authors.forename: Frann
authors.initials: F
authors.lastname: Bennett
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Whitters
authors.forename: Riyez
authors.initials: R
authors.lastname: Karim
authors.forename: Mary
authors.initials: M
authors.lastname: Collins
authors.forename: Samuel J
authors.initials: SJ
authors.lastname: Goldman
authors.forename: Kyriaki
authors.initials: K
authors.lastname: Dunussi-Joannopoulos
authors.forename: Cara M M
authors.initials: CM
authors.lastname: Williams
authors.forename: Jill F
authors.initials: JF
authors.lastname: Wright
authors.forename: Lynette A
authors.initials: LA
authors.lastname: Fouser
mesh_terms: D019264:Adoptive Transfer / Q000379:methods; D000818:Animals; D019281:Dimerization; D004195:Disease Models, Animal; D020381:Interleukin-17 / Q000096:biosynthesis* / Q000276:immunology; D008168:Lung / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D020556:Neutrophil Infiltration / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
chemical_list: D020381:Interleukin-17