Identification of the IL-17 receptor related molecule IL-17RC as the receptor for IL-17F

J Immunol. 2007 Oct 15;179(8):5462-73. doi: 10.4049/jimmunol.179.8.5462.


The proinflammatory cytokines IL-17A and IL-17F have a high degree of sequence similarity and share many biological properties. Both have been implicated as factors contributing to the progression of inflammatory and autoimmune diseases. Moreover, reagents that neutralize IL-17A significantly ameliorate disease severity in several mouse models of human disease. IL-17A mediates its effects through interaction with its cognate receptor, the IL-17 receptor (IL-17RA). We report here that the IL-17RA-related molecule, IL-17RC is the receptor for IL-17F. Notably, both IL-17A and IL-17F bind to IL-17RC with high affinity, leading us to suggest that a soluble form of this molecule may serve as an effective therapeutic antagonist of IL-17A and IL-17F. We generated a soluble form of IL-17RC and demonstrate that it effectively blocks binding of both IL-17A and IL-17F, and that it inhibits signaling in response to these cytokines. Collectively, our work indicates that IL-17RC functions as a receptor for both IL-17A and IL-17F and that a soluble version of this protein should be an effective antagonist of IL-17A and IL-17F mediated inflammatory diseases.

MeSH terms

  • Alternative Splicing / immunology
  • Animals
  • Binding, Competitive / immunology
  • Cell Line
  • Cricetinae
  • Humans
  • Inflammation Mediators / metabolism
  • Inflammation Mediators / therapeutic use
  • Interleukin-17 / antagonists & inhibitors
  • Interleukin-17 / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Molecular Sequence Data
  • Protein Binding / genetics
  • Protein Binding / immunology
  • Receptors, Interleukin-17 / genetics
  • Receptors, Interleukin-17 / metabolism*
  • Receptors, Interleukin-17 / therapeutic use
  • Species Specificity
  • Transfection


  • Inflammation Mediators
  • Interleukin-17
  • Receptors, Interleukin-17

Associated data

  • GENBANK/AX360307
  • GENBANK/AX360310
  • GENBANK/BD292072
  • GENBANK/CS251263
  • GENBANK/CS251267
  • GENBANK/EF676032
  • GENBANK/EF676033
  • GENBANK/EF676034