Improved hematopoietic stem cell transplantation upon inhibition of natural killer cell-derived interferon-gamma

Lorena Lobo de Figueiredo-Pontes, Miroslava K. Adamcova, Srdjan Grusanovic, Maria Kuzmina, Izabela Aparecida Lopes, Amanda Fernandes de Oliveira Costa, Hong Zhang, Hynek Strnad, Sanghoon Lee, Alena Moudra, Anna T. Jonasova, Michal Zidka, Robert S. Welner, Daniel G. Tenen, Meritxell Alberich-Jorda

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1999-2013
Number of pages15
JournalStem Cell Reports
Volume16
Issue number8
DOIs
StatePublished - Aug 10 2021

Keywords

  • C/EBPgamma
  • hematopoietic stem cell
  • hematopoietic stem cell transplantation
  • interferon-gamma
  • natural killer cell

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Developmental Biology
  • Cell Biology

Fingerprint

Dive into the research topics of 'Improved hematopoietic stem cell transplantation upon inhibition of natural killer cell-derived interferon-gamma'. Together they form a unique fingerprint.

Cite this