- Salima Benbarche1,
- Catherine Strassel1,
- Catherine Angénieux2,
- Léa Mallo2,
- Monique Freund2,
- Christian Gachet2,
- François Lanza1 and
- Henri de la Salle2,*
- 1 Universite' de Strasbourg, INSERM, EFS ALCA, BPPS UMR-S 949, FMTS, Strasbourg, France;
- 2 Université de Strasbourg, INSERM, EFS ALCA, BPPS UMR-S 949, FMTS, Strasbourg, France
- ↵* Corresponding author; email:
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 bone marrow 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 megakaryopoieisis and thrombopoiesis in mice. The IL-21Rα chain was expressed in human bone marrow 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 megakaryocyte 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 bone marrow 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.
- Received January 15, 2016.
- Accepted January 4, 2017.
- Copyright © 2017, Ferrata Storti Foundation