IL-17 for Therapy

J Dermatol Sci. 2017 Sep;87(3):221-227. doi: 10.1016/j.jdermsci.2017.06.010. Epub 2017 Jun 15.

Abstract

The cytokine IL-17 is now a target for an array of therapeutic monoclonal antibodies supposed to treat a variety of inflammatory diseases. The forerunner Secukinumab, an IL-17A neutralizing antibody, is meanwhile approved as first-line treatments for moderate-to-severe plaque psoriasis, and as second-line treatment for psoriatic arthritis and ankylosing spondylitis. Ixekizumab and Brodalumab, both also targeting the IL-17 pathway, were also recently approved by the FDA for plaque psoriasis. Using mice overexpressing IL-17A in a tissue of choice, we showed that the ectopic expression of this cytokine in keratinocytes resulted in a spontaneous and very strong form of psoriasis-like dermatitis. Interestingly, this model showed some typical comorbidities found in humans with psoriasis. In this review, we will discuss why IL-17 is a good target especially in psoriasis and what we learned from mouse models about its functions in pathological situations.

Keywords: Autoimmunity; IL-17; IL-17 neutralizing monoclonal antibodies; IL-17 receptor; Psoriasis.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Dermatitis / immunology*
  • Dermatitis / pathology
  • Disease Models, Animal
  • Humans
  • Interleukin-17 / antagonists & inhibitors*
  • Interleukin-17 / genetics
  • Interleukin-17 / immunology*
  • Interleukin-17 / metabolism
  • Mice
  • Mice, Transgenic
  • Molecular Targeted Therapy / methods
  • Psoriasis / drug therapy*
  • Psoriasis / immunology
  • Signal Transduction / immunology
  • Skin / immunology
  • Skin / pathology
  • Spondylitis, Ankylosing / drug therapy

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • IL17A protein, human
  • Il17a protein, mouse
  • Interleukin-17
  • brodalumab
  • ixekizumab
  • secukinumab