TY - EJOU
AU - Perdreau, Harmonie
AU - Mortier, Erwan
AU - Bouchaud, Grégory
AU - Solé, Véronique
AU - Boublik, Yvan
AU - Plet, Ariane
AU - Jacques, Yannick
TI - Different dynamics of IL-15R activation following IL-15 cis- or trans-presentation
T2 - European Cytokine Network
PY - 2010
VL - 21
IS - 4
SN - 1952-4005
AB - Interleukin (IL)-15 is a cytokine critical for the homeostasis and the function of NK cells, NK-Tcells, and memory CD8+ T cells. IL-15 signals are delivered through the IL-15Rβ and the commonγ (γc) receptorchains. The third receptor chain, IL-15Rα, confers specificity and high affinity for the cytokine. While IL-15 canactivate with high affinity the trimeric receptor expressed by a target cell (cis-presentation), IL-15Rα is alsoknown to trans-present IL-15 with high affinity to target cells expressing the IL-15Rβ/γc complex. In order tocompare the IL-15 cis- and trans-presentation processes, and using a T cell line expressing both IL-15Rα/β/γc andIL-15Rβ/γc, we analyzed cell surface receptor chain down-modulation, cytokine internalization and signalingresponses induced either with IL-15 (cis-presentation) or with RLI, a protein resulting from fusion betweenIL-15 and an extended IL-15Rα sushi domain, that mimics trans-presentation. Whereas IL-15 bound with highaffinity to IL-15Rα/β/γc, RLI bound with a similar high affinity to IL-15Rβ/γc. The kinetics of cell surfaceIL-15R down-modulation were slower following RLI treatment than after IL-15 treatment, as were the kineticsof RLI internalization, which was slower than that of IL-15. IL-15 and RLI dose-dependently induced the activa-tion of similar signaling pathways. However, the kinetics and duration of these activations were markedly differ-ent, RLI-induced signaling, being slower, but more prolonged than that induced by IL-15, although the finalproliferative responses at 48 h were similar. These findings collectively indicate that IL-15 cis- and trans-presentation mechanisms lead to different dynamics of receptor activation and signal transduction, withcis-presentation inducing fast and transient responses, and trans-presentation inducing slower, more persistentones. They provide clues for a better understanding of how IL-15 action is controlled, and how it plays a keyrole in the coordination between innate and adaptative immunity.
KW - IL-15 receptor
KW - trans-presentation
KW - binding
KW - internalization
KW - cell signaling
DO - 10.1684/ecn.2010.0207