PATHOLOGY

The interleukin 23/interleukin 17 pathway contributes to autoimmune disease pathology in experimental models and there is considerable evidence that this pathway is critical for the development of human disease:

  • Gain-of-function genetic variants (polymorphisms) in the interleukin 23 receptor are strong risk factors for the development of inflammatory bowel and psoriasis
  • Neutralizing antibodies directed towards the p19 subunit of interleukin 23 are clinically effective in psoriasis
  • Neutralizing antibodies directed against interleukin 17A and the interleukin 17 receptor are clinically effective in psoriasis and ankylosing spondylitis
  • Studies in mice where RORγt has been selectively deleted indicate that RORγt is essential for the differentiation of Th17 cells and the manifestation of disease pathology in models of autoimmune disease
  • Small molecule inhibitors of RORγt are effective in suppressing the expansion of Th17 cells in vitro and in vivo