Targeting Th17 cells in autoimmune diseases

Trends Pharmacol Sci. 2014 Oct;35(10):493-500. doi: 10.1016/ Epub 2014 Aug 14.


T helper 17 (Th17) cells have been implicated in the pathogenesis of most common autoimmune diseases, including psoriasis, rheumatoid arthritis (RA), inflammatory bowel disease (IBD), and multiple sclerosis (MS). Although anti-interleukin-17 (IL-17) antibodies show marked clinical efficacy in psoriasis, targeting IL-17 alone is not sufficient to improve clinical end points in other autoimmune conditions, namely RA and Crohn's disease. Given that Th17 cells express IL-17 together with many other proinflammatory cytokines [IL-17F, IL-22, IL-26, and granulocyte-macrophage colony-stimulating factor (GM-CSF)], targeting the Th17 cell lineage may be superior to blocking a single effector cytokine. Here, we discuss the rationale for targeting two checkpoints in the development and inflammatory function of Th17 cells, retinoid-related orphan receptor-γt (RORγt) and IL-23, and we review recent progress in the development of both RORγt small molecule inhibitors and IL-23 neutralizing antibodies.

Keywords: IL-17; IL-23; RORγt; autoimmune diseases.

Publication types

  • Review

MeSH terms

  • Animals
  • Autoimmune Diseases / drug therapy*
  • Autoimmune Diseases / immunology*
  • Drug Delivery Systems
  • Humans
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / antagonists & inhibitors
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / immunology
  • Small Molecule Libraries / pharmacology
  • Th17 Cells / drug effects*
  • Th17 Cells / immunology*


  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • Small Molecule Libraries