The multifaceted regulation of interleukin-15 expression and the role of this cytokine in NK cell differentiation and host response to intracellular pathogens

Annu Rev Immunol. 1999;17:19-49. doi: 10.1146/annurev.immunol.17.1.19.


Interleukin-15 (IL-15) is a 14- to 15-kDa member of the 4 alpha-helix bundle family of cytokines. IL-15 expression is controlled at the levels of transcription, translation, and intracellular trafficking. In particular, IL-15 protein is posttranscriptionally regulated by multiple controlling elements that impede translation, including 12 upstream AUGs of the 5' UTR, 2 unusual signal peptides, and the C-terminus of the mature protein. IL-15 uses two distinct receptor and signaling pathways. In T and NK cells the IL-15 receptor includes IL-2/15R beta and gamma c subunits, which are shared with IL-2, and an IL-15-specific receptor subunit, IL-15R alpha. Mast cells respond to IL-15 with a receptor system that does not share elements with the IL-2 receptor but uses a novel 60- to 65-kDa IL-15RX subunit. In mast cells IL-15 signaling involves Jak2/STAT5 activation rather than the Jak1/Jak3 and STAT5/STAT3 system used in activated T cells. In addition to its other functional activities in immune and nonimmune cells, IL-15 plays a pivotal role in the development, survival, and function of NK cells. Abnormalities of IL-15 expression have been described in patients with rheumatoid arthritis or inflammatory bowel disease and in diseases associated with the retroviruses HIV and HTLV-I. New approaches directed toward IL-15, its receptor, or its signaling pathway may be of value in the therapy of these disorders.

Publication types

  • Review

MeSH terms

  • Animals
  • Autoimmune Diseases / immunology
  • Base Sequence
  • Cell Differentiation
  • DNA, Complementary / genetics
  • Gene Expression Regulation
  • Humans
  • Immunosuppression Therapy
  • Immunotherapy
  • Inflammation / immunology
  • Interleukin-15 / genetics*
  • Interleukin-15 / physiology*
  • Killer Cells, Natural / cytology
  • Killer Cells, Natural / immunology*
  • Neoplasms / immunology
  • Receptors, Interleukin-15
  • Receptors, Interleukin-2 / physiology
  • Retroviridae Infections / immunology
  • Signal Transduction


  • DNA, Complementary
  • IL15RA protein, human
  • Interleukin-15
  • Receptors, Interleukin-15
  • Receptors, Interleukin-2