Dual role of IL-21 in megakaryopoiesis and platelet homeostasis.
Fiche publication
Date publication
avril 2017
Journal
Haematologica
Auteurs
Membres identifiés du Cancéropôle Est :
Dr GACHET Christian
Tous les auteurs :
Benbarche S, Strassel C, Angénieux C, Mallo L, Freund M, Gachet C, Lanza F, de la Salle H
Lien Pubmed
Résumé
Gene profiling studies have indicated that differentiated human megakaryocytes express the receptor for IL-21 (IL-21R), an immunostimulatory cytokine associated with inflammatory disorders and currently under evaluation in cancer therapy. The aim of this study was to investigate whether IL-21 modulates megakaryopoiesis. We first checked the expression of IL-21 receptor on human bone marrow and differentiated megakaryocytes. We then investigated the effect of IL-21 on the differentiation of human blood CD34 progenitors into megakaryocytes. Finally, we analyzed the consequences of hydrodynamic transfection-mediated transient expression of IL-21, on megakaryopoiesis and thrombopoiesis in mice. The IL-21Rα chain was expressed in human bone marrow megakaryocytes and was progressively induced during differentiation of human peripheral CD34 progenitors, while the signal transducing γ chain was down-regulated. Consistently, the STAT3 phosphorylation induced by IL-21 diminished during the later stages of megakaryocytic differentiation. , IL-21 increased the number of colony-forming unit megakaryocytes generated from CD34 cells and the number of megakaryocytes differentiated from CD34 progenitors in a JAK3- and STAT3-dependent manner. Forced expression of IL-21 in mice increased the density of bi-potent megakaryocyte progenitors and bone marrow megakaryocytes, and the platelet generation, but increased platelet clearance with a consequent reduction in blood cell counts. Our work suggests that IL-21 regulates megakaryocyte development and platelet homeostasis. Thus, IL-21 may link immune responses to physiological or pathological platelet-dependent processes.
Mots clés
Animals, Blood Platelets, metabolism, Cell Differentiation, drug effects, Cell Proliferation, Gene Expression, Homeostasis, Humans, Interleukins, genetics, Janus Kinase 3, metabolism, Megakaryocyte Progenitor Cells, cytology, Megakaryocytes, cytology, Mice, Phenotype, Receptors, Interleukin-21, genetics, STAT3 Transcription Factor, metabolism, Signal Transduction, drug effects, Thrombopoiesis, drug effects
Référence
Haematologica. 2017 04;102(4):637-646