Interleukin 17A: Toward a New Understanding of Psoriasis Pathogenesis

J Am Acad Dermatol. 2014 Jul;71(1):141-50. doi: 10.1016/j.jaad.2013.12.036. Epub 2014 Mar 18.

Abstract

Molecular and cellular understanding of psoriasis pathogenesis has evolved considerably over the last 30 years beginning in the early 1980s when psoriasis was thought to be a skin disease driven by keratinocyte hyperproliferation. During the next 20 years, the role of the immune system and T-helper (Th) cells in psoriasis pathogenesis was recognized. The presence of the interleukin (IL)-12 cytokine in psoriatic lesions led to the postulate that psoriasis is mediated by Th1 cells. Recent evidence has revealed a role for Th17 cells, and other immune cells, as proximal regulators of psoriatic skin inflammation. IL-17A, the principal effector cytokine of Th17 cells, stimulates keratinocytes to produce chemokines, cytokines, and other proinflammatory mediators thereby enabling IL-17A to bridge the innate and adaptive immune systems to sustain chronic inflammation. This model underlies the rationale for inhibiting IL-17A signaling as a potential therapeutic approach to disrupt the psoriatic inflammatory loop. Several monoclonal antibodies that inhibit the IL-17 pathway are in clinical development. These agents exhibit promising clinical efficacy and tolerability profiles including immunohistochemical improvement in psoriatic plaques. Results from clinical trials with IL-17 pathway inhibitors are refining our understanding of psoriasis pathogenesis and may provide a new therapeutic approach for patients with moderate to severe psoriasis.

Keywords: T-helper 17 cells; T-helper 1 cells; cytokines; interleukin-17A; interleukin-23; keratinocytes; pathogenesis; psoriasis.

Publication types

  • Historical Article
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antibodies, Monoclonal / therapeutic use
  • Dendritic Cells / immunology
  • History, 20th Century
  • History, 21st Century
  • Humans
  • Immunohistochemistry
  • Interleukin-17 / antagonists & inhibitors
  • Interleukin-17 / immunology*
  • Models, Immunological*
  • Psoriasis / drug therapy*
  • Psoriasis / history
  • Psoriasis / immunology*
  • Psoriasis / metabolism
  • Th17 Cells / drug effects
  • Th17 Cells / immunology*
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors

Substances

  • Antibodies, Monoclonal
  • IL17A protein, human
  • Interleukin-17
  • Tumor Necrosis Factor-alpha