title: Regulation of inflammatory responses by IL-17F.
abstract: Although interleukin (IL) 17 has been extensively characterized, the function of IL-17F, which has an expression pattern regulated similarly to IL-17, is poorly understood. We show that like IL-17, IL-17F regulates proinflammatory gene expression in vitro, and this requires IL-17 receptor A, tumor necrosis factor receptor-associated factor 6, and Act1. In vivo, overexpression of IL-17F in lung epithelium led to infiltration of lymphocytes and macrophages and mucus hyperplasia, similar to observations made in IL-17 transgenic mice. To further understand the function of IL-17F, we generated and analyzed mice deficient in IL-17F or IL-17. IL-17, but not IL-17F, was required for the initiation of experimental autoimmune encephalomyelitis. Mice deficient in IL-17F, but not IL-17, had defective airway neutrophilia in response to allergen challenge. Moreover, in an asthma model, although IL-17 deficiency reduced T helper type 2 responses, IL-17F-deficient mice displayed enhanced type 2 cytokine production and eosinophil function. In addition, IL-17F deficiency resulted in reduced colitis caused by dextran sulfate sodium, whereas IL-17 knockout mice developed more severe disease. Our results thus demonstrate that IL-17F is an important regulator of inflammatory responses that seems to function differently than IL-17 in immune responses and diseases.
authors.affiliation: Department of Immunology, MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Xuexian O
authors.initials: XO
authors.lastname: Yang
authors.forename: Seon Hee
authors.initials: SH
authors.lastname: Chang
authors.forename: Heon
authors.initials: H
authors.lastname: Park
authors.forename: Roza
authors.initials: R
authors.lastname: Nurieva
authors.forename: Bhavin
authors.initials: B
authors.lastname: Shah
authors.forename: Luis
authors.initials: L
authors.lastname: Acero
authors.forename: Yi-Hong
authors.initials: YH
authors.lastname: Wang
authors.forename: Kimberly S
authors.initials: KS
authors.lastname: Schluns
authors.forename: Russell R
authors.initials: RR
authors.lastname: Broaddus
authors.forename: Zhou
authors.initials: Z
authors.lastname: Zhu
authors.forename: Chen
authors.initials: C
authors.lastname: Dong
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D005347:Fibroblasts / Q000166:cytology / Q000276:immunology; D006706:Homeostasis / Q000276:immunology; D007249:Inflammation / Q000276:immunology*; D020381:Interleukin-17 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008213:Lymphocyte Activation; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology*; D014162:Transfection
chemical_list: D020381:Interleukin-17