IL-15/IL-15R alpha intracellular trafficking in human cells and protection from apoptosis

Ann N Y Acad Sci. 1999 Jun 22;876:236-45. doi: 10.1111/j.1749-6632.1999.tb07644.x.

Abstract

IL-15 is an immunostimulatory cytokine sharing with IL-2 the IL-2R beta gamma complex. In vivo, IL-15 detection in synovial fluids has been associated with the development of rheumatoid arthritis. A debate exists as to whether IL-15 has the potential to be secreted in meaningful amounts or to act as a pericellular cytokine. Our data show (1) the presence of two IL-15 isoforms displaying signal peptides of different length and the capacity to be secreted restricted to the isoform bearing the longer one; (2) in cells expressing the two isoforms, the existence of different nuclear localization and intracellular trafficking of IL-15 and IL-15R alpha; and (3) an intercellular microcirculation of IL-15, not detectable with ELISA kits, but displaying a role as an anti-apoptotic factor able to induce the deflection of the TNFR associated factor 2 (TRAF) to IL-15R alpha. Our data point to a juxtacrine mechanism of action of IL-15 and suggest a role for IL-15/IL-15R alpha in the regulation of apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / physiology*
  • CHO Cells
  • Cricetinae
  • Humans
  • Interleukin-15 / metabolism*
  • Intracellular Membranes / metabolism*
  • Microscopy, Confocal
  • Protein Isoforms / metabolism
  • Proteins / metabolism
  • Receptors, Interleukin-15
  • Receptors, Interleukin-2 / metabolism*
  • TNF Receptor-Associated Factor 2
  • Tissue Distribution / physiology
  • Tumor Cells, Cultured

Substances

  • IL15RA protein, human
  • Interleukin-15
  • Protein Isoforms
  • Proteins
  • Receptors, Interleukin-15
  • Receptors, Interleukin-2
  • TNF Receptor-Associated Factor 2