TY - JOUR
T1 - Membrane-bound and soluble IL-15/IL-15Rα complexes display differential signaling and functions on human hematopoietic progenitors
AU - Giron-Michel, Julien
AU - Giuliani, Massimo
AU - Fogli, Manuela
AU - Brouty-Boýe, Danièle
AU - Ferrini, Silvano
AU - Baychelier, Florence
AU - Eid, Pierre
AU - Lebousse-Kerdilès, Caroline
AU - Durali, Deniz
AU - Biassoni, Roberto
AU - Charpentier, Bernard
AU - Vasquez, Aimé
AU - Chouaib, Salem
AU - Caignard, Anne
AU - Moretta, Lorenzo
AU - Azzarone, Bruno
PY - 2005/10
Y1 - 2005/10
N2 - Membrane-bound and soluble interleukin-15 (IL-15)/IL-15 receptor α (Rα) complexes trigger differential transcription factor activation and functions on human hematopoietic progenitors. Indeed, human spleen myofibroblasts (SMFs) are characterized by a novel mechanism of IL-15 trans-presentation (SMFmb [membrane-bound]-IL-15), based on the association of an endogenous IL-15/IL-15Rα complex with the IL-15Rβγc chains. SMFmb-IL-15 (1) induces lineage-specific signaling pathways that differ from those controlled by soluble IL-15 in unprimed and committed normal progenitors; (2) triggers survival and proliferation of leukemic progenitors expressing low-affinity IL-15R (M07Sb cells); (3) causes only an antiapoptotic effect on leukemic cells expressing high-affinity receptors (TF1β cells). This behavior is likely due to the IL-15Rα chain present on these cells that interact with the SMFmb-IL-15, inhibiting signal transducer and transcriptional activator 5 (STAT5) activation. On the other hand, the soluble IL-15/IL-15Rα complex (hyper IL-15) displays a dominant pattern of action, activating only those cells expressing low-affinity IL-15R (IL- 15Rβγc). Thus, hyper IL-15 induces antiapoptotic effects on M075b cells and the up-regulation of STAT6 activation on adult peripheral blood (PB) pre-natural killer (NK) committed progenitors. The latter effect using 100-fold concentrations of recombinant (r)-IL-15. In conclusion, SMFmb-IL-15 and soluble IL-15Rα/IL-15 complexes seem to play a pivotal role in the control of the survival, proliferation and differentiation of both normal and leukemic circulating progenitors, highlighting new functions of IL-15 and of IL-15Rα.
AB - Membrane-bound and soluble interleukin-15 (IL-15)/IL-15 receptor α (Rα) complexes trigger differential transcription factor activation and functions on human hematopoietic progenitors. Indeed, human spleen myofibroblasts (SMFs) are characterized by a novel mechanism of IL-15 trans-presentation (SMFmb [membrane-bound]-IL-15), based on the association of an endogenous IL-15/IL-15Rα complex with the IL-15Rβγc chains. SMFmb-IL-15 (1) induces lineage-specific signaling pathways that differ from those controlled by soluble IL-15 in unprimed and committed normal progenitors; (2) triggers survival and proliferation of leukemic progenitors expressing low-affinity IL-15R (M07Sb cells); (3) causes only an antiapoptotic effect on leukemic cells expressing high-affinity receptors (TF1β cells). This behavior is likely due to the IL-15Rα chain present on these cells that interact with the SMFmb-IL-15, inhibiting signal transducer and transcriptional activator 5 (STAT5) activation. On the other hand, the soluble IL-15/IL-15Rα complex (hyper IL-15) displays a dominant pattern of action, activating only those cells expressing low-affinity IL-15R (IL- 15Rβγc). Thus, hyper IL-15 induces antiapoptotic effects on M075b cells and the up-regulation of STAT6 activation on adult peripheral blood (PB) pre-natural killer (NK) committed progenitors. The latter effect using 100-fold concentrations of recombinant (r)-IL-15. In conclusion, SMFmb-IL-15 and soluble IL-15Rα/IL-15 complexes seem to play a pivotal role in the control of the survival, proliferation and differentiation of both normal and leukemic circulating progenitors, highlighting new functions of IL-15 and of IL-15Rα.
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U2 - 10.1182/blood-2005-01-0064
DO - 10.1182/blood-2005-01-0064
M3 - Article
C2 - 15976182
AN - SCOPUS:27144446158
VL - 106
SP - 2302
EP - 2310
JO - Blood
JF - Blood
SN - 0006-4971
IS - 7
ER -