Membrane-bound and soluble IL-15/IL-15Rα complexes display differential signaling and functions on human hematopoietic progenitors

Julien Giron-Michel, Massimo Giuliani, Manuela Fogli, Danièle Brouty-Boýe, Silvano Ferrini, Florence Baychelier, Pierre Eid, Caroline Lebousse-Kerdilès, Deniz Durali, Roberto Biassoni, Bernard Charpentier, Aimé Vasquez, Salem Chouaib, Anne Caignard, Lorenzo Moretta, Bruno Azzarone

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)2302-2310
Number of pages9
JournalBlood
Volume106
Issue number7
DOIs
Publication statusPublished - Oct 2005

ASJC Scopus subject areas

  • Hematology

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    Giron-Michel, J., Giuliani, M., Fogli, M., Brouty-Boýe, D., Ferrini, S., Baychelier, F., Eid, P., Lebousse-Kerdilès, C., Durali, D., Biassoni, R., Charpentier, B., Vasquez, A., Chouaib, S., Caignard, A., Moretta, L., & Azzarone, B. (2005). Membrane-bound and soluble IL-15/IL-15Rα complexes display differential signaling and functions on human hematopoietic progenitors. Blood, 106(7), 2302-2310. https://doi.org/10.1182/blood-2005-01-0064