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Cited by 18Platelet Disorders and TreatmentsCytokine Signaling Pathways and InteractionsBlood Coagulation and Thrombosis Mechanisms

Dual role of IL-21 in megakaryopoiesis and platelet homeostasis

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Benbarche, Salima, Strassel, Catherine, Angénieux, Catherine, Mallo, Léa, Freund, Monique, Gachet, Christian, Lanza, François, de la Salle, Henri·2017·Haematologica
DOI 10.3324/haematol.2016.143958PMC PMC5395104
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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 bone marrow and in vitro differentiated megakaryocytes. We then 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 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 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.

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Cited by

Sorted by citations

Authors
Benbarche, S., Strassel, C., Angénieux, C., Mallo, L., Freund, M., Gachet, C., Lanza, F., & de la Salle, H.
Affiliations
Inserm (FR)
ORCID
Venue
Haematologica
Publisher
Ferrata Storti Foundation (Haematologica)
Published
2017-01-05
Volume
102
Issue
4
Pages
637-646
ISSN
  • 0390-6078 (ISSN-L)
  • 1592-8721
DOI
10.3324/haematol.2016.143958
PMC
PMC5395104
OpenAlex
W2568284630
Cited by
18
References
1
Citations by year
2025: 3 · 2024: 3 · 2023: 1 · 2022: 1 · 2021: 5 · 2020: 2 · 2019: 1 · 2018: 2
FWCI
1.05
Type
journal article
Language
en
Open access
Locations
  • Haematologica (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Topics
  • Health Sciences › Medicine › Hematology › Platelet Disorders and Treatments
  • Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
  • Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
Keywords
IL-21, IL-21 receptor, megakaryopoiesis, platelet homeostasis, STAT3 signaling, JAK3, CD34+ progenitors, platelet clearance, bone marrow megakaryocytes
MeSH terms
Interleukin-21, Animals, Blood Platelets, Cell Differentiation, Homeostasis, Humans, Interleukins, Megakaryocytes, Phenotype, Signal Transduction, Gene Expression, Thrombopoiesis, Cell Proliferation, STAT3 Transcription Factor, Mice, Janus Kinase 3, Receptors, Interleukin-21, Megakaryocyte Progenitor Cells

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