Interleukin-21 as a new therapeutic target for immune-mediated diseases

Trends Pharmacol Sci. 2009 Aug;30(8):441-7. doi: 10.1016/ Epub 2009 Jul 16.


Cytokines have a decisive role in initiating and shaping pathologic responses in patients with various immune-inflammatory diseases. Recent studies indicate that interleukin (IL)-21, a cytokine produced mostly by activated CD4+ T cells, participates in the tissue damage in various tissues, owing to its ability to regulate the function of immune and non-immune cells. For instance, IL-21 controls the differentiation and functional activity of T cells, B cells and NK cells, limits the differentiation of inducible regulatory T cells (Tregs), and makes T cells resistant to the Treg-mediated immunesuppression. It also stimulates epithelial cells and fibroblasts to produce inflammatory mediators. Here, we focus on data supporting the pathogenic role of IL-21 in human inflammatory diseases and discuss pre-clinical studies that suggest that neutralization of IL-21 in vivo could be a new biological therapy to combat immune-mediated pathologies, such as inflammatory bowel diseases, diabetes, rheumatoid arthritis and systemic lupus erythematosus.

Publication types

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

MeSH terms

  • Animals
  • Autoimmune Diseases / drug therapy
  • Autoimmune Diseases / physiopathology
  • Disease Models, Animal
  • Drug Delivery Systems
  • Humans
  • Immune System Diseases / drug therapy*
  • Immune System Diseases / immunology
  • Immune System Diseases / physiopathology*
  • Immunosuppressive Agents / therapeutic use*
  • Inflammation / drug therapy*
  • Inflammation / physiopathology
  • Interleukins / antagonists & inhibitors
  • Interleukins / immunology
  • Interleukins / physiology*
  • Models, Immunological
  • Signal Transduction / physiology


  • Immunosuppressive Agents
  • Interleukins
  • interleukin-21