Regulation of inflammatory responses by IL-17F

Xuexian O. Yang, Hee Chang Seon, Heon Park, Roza Nurieva, Bhavin Shah, Luis Acero, Yi Hong Wang, Kimberly S. Schluns, Russell R. Broaddus, Zhou Zhu, Chen Dong

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)1063-1075
Number of pages13
JournalJournal of Experimental Medicine
Volume205
Issue number5
DOIs
StatePublished - May 12 2008

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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