Anti-CD69 therapy induces rapid mobilization and high proliferation of HSPCs through S1P and mTOR.

Leukemia
Laura NotarioPilar Lauzurica

Abstract

CD69 regulates lymphocyte egress from the thymus and lymph nodes through cis-interactions and the downregulation of surface sphingosine-1-phosphate (S1P) receptor-1 (S1P1). However, its role in the regulation of cell egress from bone marrow has not been extensively studied. We show here that CD69 targeting induced rapid and massive mobilization of BM leukocytes, which was inhibited by desensitization to S1P with FTY720. This mobilization was reproduced with anti-human CD69 mAb treatment of mice expressing human CD69. In this strain, the mobilization occurred to the same extent as that induced by AMD3100. The anti-human CD69 treatment highly increased LSK and CLP cell proliferation and numbers, both in the periphery and in the BM, and also augmented S1P1 and CXCR4 expression. Additionally, increased mTOR, p70S6K, S6, and 4E-BP1 phosphorylation was detected after in vivo anti-CD69 treatment in the bone marrow. Importantly, mTOR inhibition with rapamycin inhibited anti-huCD69-induced mobilization of hematopoietic stem and progenitor cells (HSPCs). Together, our results indicated that CD69 targeting induces not only mobilization but also high proliferation of HSPCs, and thus is crucial for precursor cell replenishment over time. Th...Continue Reading

References

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Citations

Jan 28, 2020·Journal of Leukocyte Biology·Wenxiao ZhangMandy L Ford
Jul 19, 2019·Journal of Virology·Laura NotarioPilar Lauzurica
Jul 26, 2018·Leukemia·Nir BujanoverRoi Gazit
Nov 17, 2020·Frontiers in Genetics·Jennifer Redondo-AntónPilar Lauzurica
Feb 16, 2021·Stem Cell Reviews and Reports·Hélia FernandesEugénia Carvalho
Apr 15, 2021·Proceedings of the National Academy of Sciences of the United States of America·Thiago Alves da CostaRoberta Pelanda

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Methods Mentioned

BETA
ELISA
flow cytometry
transgenic

Software Mentioned

FlowJo
SPSS
GraphPad Prism
BD FacsDiva

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