The biology of IL-15: implications for cancer therapy and the treatment of autoimmune disorders

J Investig Dermatol Symp Proc. 2013 Dec;16(1):S28-30. doi: 10.1038/jidsymp.2013.8.

Abstract

IL-15 has a pivotal role in life and death of natural killer (NK) and CD8 memory T cells. IL-15 signals through a heterotrimeric receptor involving the common gamma chain (γc) shared with IL-2, IL-4, IL-7, IL-9, and IL-21, IL-2/IL-15 receptor β (IL-15Rβ) shared with IL-2 and a private IL-15Rα subunit. IFN- or CD40 ligand-stimulated dendritic cells coordinately express IL-15 and IL-15Rα. Cell surface IL-15Rα presents IL-15 in trans to cells that express IL-2/IL-15Rβ and γc. IL-15 is being used to treat patients with metastatic malignancy. However, IL-15 is an inflammatory cytokine involved in immunological memory including that to self, thereby playing a role in autoimmune diseases. These insights provide the scientific basis for clinical strategies directed toward diminishing IL-15 action. Dysregulated IL-15 expression was demonstrated in patients with rheumatoid arthritis, inflammatory bowel disease, psoriasis, celiac disease, and alopecia areata. The monoclonal antibody Hu-Mik-β-1 targets the cytokine receptor subunit IL-2/IL-15Rβ (CD122), blocks IL-15 transpresentation, and is being used in clinical trials in patients with autoimmune diseases. In parallel, clinical trials have been initiated involving the Jak2/3 (Janus kinase-2/3) inhibitor tofacitinib and Jak1/2 inhibitor ruxolitinib to block IL-15 signaling.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alopecia Areata / drug therapy
  • Animals
  • Antibodies, Monoclonal / therapeutic use*
  • Autoimmune Diseases / drug therapy*
  • Autoimmune Diseases / metabolism
  • Humans
  • Interleukin-15 / immunology*
  • Interleukin-15 / metabolism*
  • Leukemia-Lymphoma, Adult T-Cell / drug therapy
  • Neoplasms / drug therapy*
  • Piperidines / therapeutic use
  • Protein Kinase Inhibitors / therapeutic use
  • Pyrimidines / therapeutic use
  • Pyrroles / therapeutic use
  • Receptors, Interleukin-15 / metabolism
  • Signal Transduction

Substances

  • Antibodies, Monoclonal
  • Hu-Mik-beta-1 monoclonal antibody
  • Interleukin-15
  • Piperidines
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Pyrroles
  • Receptors, Interleukin-15
  • tofacitinib