TY - JOUR
T1 - Improved hematopoietic stem cell transplantation upon inhibition of natural killer cell-derived interferon-gamma
AU - Lobo de Figueiredo-Pontes, Lorena
AU - Adamcova, Miroslava K.
AU - Grusanovic, Srdjan
AU - Kuzmina, Maria
AU - Aparecida Lopes, Izabela
AU - Fernandes de Oliveira Costa, Amanda
AU - Zhang, Hong
AU - Strnad, Hynek
AU - Lee, Sanghoon
AU - Moudra, Alena
AU - Jonasova, Anna T.
AU - Zidka, Michal
AU - Welner, Robert S.
AU - Tenen, Daniel G.
AU - Alberich-Jorda, Meritxell
N1 - Funding Information:
This work was supported by a grant from São Paulo Research Foundation ( FAPESP ; grant 2015/21866-1 ) to L.L.d.F.-P. M.A.-J. was supported by a GACR grant 18-08577S and institutional funding from the IMG CAS (RVO 68378050 ). D.G.T. was supported by a STaR Investigator Award, an RCE Core grant, and Tier 3 RNA Biology Center grant MOE2014-T3-1-006 from the NRF and MOE , Singapore, and NIH grants R35CA197697 and P01HL131477 . The authors thank Prof. Vaclav Horejsi for providing us with the IFNγ and IgG1 antibodies.
Publisher Copyright:
© 2021 The Authors
PY - 2021/8/10
Y1 - 2021/8/10
N2 - Hematopoietic stem cell transplantation (HSCT) is a frequent therapeutic approach to restore hematopoiesis in patients with hematologic diseases. Patients receive a hematopoietic stem cell (HSC)-enriched donor cell infusion also containing immune cells, which may have a beneficial effect by eliminating residual neoplastic cells. However, the effect that donor innate immune cells may have on the donor HSCs has not been deeply explored. Here, we evaluate the influence of donor natural killer (NK) cells on HSC fate, concluded that NK cells negatively affect HSC frequency and function, and identified interferon-gamma (IFNγ) as a potential mediator. Interestingly, improved HSC fitness was achieved by NK cell depletion from murine and human donor infusions or by blocking IFNγ activity. Thus, our data suggest that suppression of inflammatory signals generated by donor innate immune cells can enhance engraftment and hematopoietic reconstitution during HSCT, which is particularly critical when limited HSC numbers are available and the risk of engraftment failure is high.
AB - Hematopoietic stem cell transplantation (HSCT) is a frequent therapeutic approach to restore hematopoiesis in patients with hematologic diseases. Patients receive a hematopoietic stem cell (HSC)-enriched donor cell infusion also containing immune cells, which may have a beneficial effect by eliminating residual neoplastic cells. However, the effect that donor innate immune cells may have on the donor HSCs has not been deeply explored. Here, we evaluate the influence of donor natural killer (NK) cells on HSC fate, concluded that NK cells negatively affect HSC frequency and function, and identified interferon-gamma (IFNγ) as a potential mediator. Interestingly, improved HSC fitness was achieved by NK cell depletion from murine and human donor infusions or by blocking IFNγ activity. Thus, our data suggest that suppression of inflammatory signals generated by donor innate immune cells can enhance engraftment and hematopoietic reconstitution during HSCT, which is particularly critical when limited HSC numbers are available and the risk of engraftment failure is high.
KW - C/EBPgamma
KW - hematopoietic stem cell
KW - hematopoietic stem cell transplantation
KW - interferon-gamma
KW - natural killer cell
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U2 - 10.1016/j.stemcr.2021.06.008
DO - 10.1016/j.stemcr.2021.06.008
M3 - Article
C2 - 34242616
AN - SCOPUS:85111928821
SN - 2213-6711
VL - 16
SP - 1999
EP - 2013
JO - Stem Cell Reports
JF - Stem Cell Reports
IS - 8
ER -