Dual role of IL-21 in megakaryopoiesis and platelet homeostasis: Modulation of platelet homeostasis by IL-21

Abstract : Gene profiling studies have indicated that in vitro 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 BM and in vitro differentiated megakaryocytes. Then, we investigated the effect of IL-21 on the in vitro 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 BM megakaryocytes and was progressively induced during in vitro 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. In vitro, IL-21 increased the number of CFU-MKs 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 MK progenitors and BM megakaryocytes, and the platelet generation, but increased platelet clearance and consequently resulting in reduced blood platelet 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.
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http://www.hal.inserm.fr/inserm-01431024
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Soumis le : mardi 10 janvier 2017 - 15:00:06
Dernière modification le : mercredi 14 mars 2018 - 16:40:52
Document(s) archivé(s) le : mardi 11 avril 2017 - 15:17:14

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Salima Benbarche, Catherine Strassel, Catherine Angénieux, Lea Mallo, Monique Freund, et al.. Dual role of IL-21 in megakaryopoiesis and platelet homeostasis: Modulation of platelet homeostasis by IL-21. Haematologica, Ferrata Storti Foundation, 2017, [Epub ahead of print]. 〈10.3324/haematol.2016.143958〉. 〈inserm-01431024〉

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