IL-15/IL-15R alpha intracellular trafficking in human cells and protection from apoptosis.
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.
Pereno
R
R
U506 INSERM, Hôpital Paul Brousse, Villejuif, France.
Gaggero
A
A
Scudeletti
M
M
Lanza
L
L
Meazza
R
R
Mishal
Z
Z
Jasmin
C
C
Indiveri
F
F
Ferrini
S
S
Azzarone
B
B
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D016466:CHO Cells; D006224:Cricetinae; D006801:Humans; D019409:Interleukin-15 / Q000378:metabolism*; D007425:Intracellular Membranes / Q000378:metabolism*; D018613:Microscopy, Confocal; D020033:Protein Isoforms / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2 / Q000378:metabolism*; D047992:TNF Receptor-Associated Factor 2; D014018:Tissue Distribution / Q000502:physiology; D014407:Tumor Cells, Cultured
C508024:IL15RA protein, human; D019409:Interleukin-15; D020033:Protein Isoforms; D011506:Proteins; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2; D047992:TNF Receptor-Associated Factor 2