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

Raffaele Pereno, Alessia Gaggero, Marco Scudeletti, Lorella Lanza, Raffaella Meazza, Zohar Mishal, Claude Jasmin, Francesco Indiveri, Silvano Ferrini, Bruno Azzarone

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Abstract

IL-15 is an immunostimulatory cytokine sharing with IL-2 the IL-2Rβγ 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-15Rα; 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-15Rα. Our data point to a juxtacrine mechanism of action of IL-15 and suggest a role for IL-15/IL-15Rα in the regulation of apoptosis.

Original languageEnglish
Pages (from-to)236-245
Number of pages10
JournalAnnals of the New York Academy of Sciences
Volume876
DOIs
Publication statusPublished - 1999

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Pereno, R., Gaggero, A., Scudeletti, M., Lanza, L., Meazza, R., Mishal, Z., Jasmin, C., Indiveri, F., Ferrini, S., & Azzarone, B. (1999). IL-15/IL-15Rα intracellular trafficking in human cells and protection from apoptosis. Annals of the New York Academy of Sciences, 876, 236-245. https://doi.org/10.1111/j.1749-6632.1999.tb07644.x