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Blood, 1 October 2005, Vol. 106, No. 7, pp. 2302-2310. Prepublished online as a Blood First Edition Paper on June 23, 2005; DOI 10.1182/blood-2005-01-0064. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-01-0064v1 106/7/2302    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Giron-Michel, J. Articles by Azzarone, B. Search for Related Content PubMed PubMed Citation Articles by Giron-Michel, J. Articles by Azzarone, B. Related Collections Signal Transduction Hematopoiesis and Stem Cells Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS Membrane-bound and soluble IL-15/IL-15R complexes display differential signaling and functions on human hematopoietic progenitors Julien Giron-Michel, Massimo Giuliani, Manuela Fogli, Danièle Brouty-Boyé, Silvano Ferrini, Florence Baychelier, Pierre Eid, Caroline Lebousse-Kerdilès, Deniz Durali, Roberto Biassoni, Bernard Charpentier, Aimé Vasquez, Salem Chouaib, Anne Caignard, Lorenzo Moretta, and Bruno Azzarone From the Medicina Istituto Gaslini and the Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy; U 542 and U 602 Institut National de la Santé et de la Recherche Médical (INSERM) Hôpital Paul Brousse; Laboratoire d'Oncologie Virale, Unité Propre de Recherche (UPR) 9045, Centre National de la Recherche Scientifique (CNRS); and U 487 INSERM, Institut Gustave Roussy (IGR); Villejuif, France. Membrane-bound and soluble interleukin-15 (IL-15)/IL-15 receptor (R) 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-15R complex with the IL-15Rc 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 (TF1 cells). This behavior is likely due to the IL-15R 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-15R complex (hyper IL-15) displays a dominant pattern of action, activating only those cells expressing low-affinity IL-15R (IL-15Rc). 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-15R/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-15R. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. Badoual, G. Bouchaud, N. E. H. Agueznay, E. Mortier, S. Hans, A. Gey, F. Fernani, S. Peyrard, P. L. -Puig, P. Bruneval, et al. The Soluble {alpha} Chain of Interleukin-15 Receptor: A Proinflammatory Molecule Associated with Tumor Progression in Head and Neck Cancer Cancer Res., May 15, 2008; 68(10): 3907 - 3914. [Abstract] [Full Text] [PDF] D. de Totero, R. Meazza, M. Capaia, M. Fabbi, B. Azzarone, E. Balleari, M. Gobbi, G. Cutrona, M. Ferrarini, and S. Ferrini The opposite effects of IL-15 and IL-21 on CLL B cells correlate with differential activation of the JAK/STAT and ERK1/2 pathways Blood, January 15, 2008; 111(2): 517 - 524. [Abstract] [Full Text] [PDF] T. A. Stoklasek, K. S. Schluns, and L. Lefrancois Combined IL-15/IL-15R{alpha} Immunotherapy Maximizes IL-15 Activity In Vivo J. Immunol., November 1, 2006; 177(9): 6072 - 6080. [Abstract] [Full Text] [PDF] M. P. Rubinstein, M. Kovar, J. F. Purton, J.-H. Cho, O. Boyman, C. D. Surh, and J. Sprent Converting IL-15 to a superagonist by binding to soluble IL-15R{alpha} PNAS, June 13, 2006; 103(24): 9166 - 9171. [Abstract] [Full Text] [PDF] E. Mortier, A. Quemener, P. Vusio, I. Lorenzen, Y. Boublik, J. Grotzinger, A. Plet, and Y. Jacques Soluble Interleukin-15 Receptor {alpha} (IL-15R{alpha})-sushi as a Selective and Potent Agonist of IL-15 Action through IL-15Rbeta/{gamma}: HYPERAGONIST IL-15{middle dot}IL-15R{alpha} FUSION PROTEINS J. Biol. Chem., January 20, 2006; 281(3): 1612 - 1619. [Abstract] [Full Text] [PDF]

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