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

0555012 - ÚMG 2022 RIV US eng J - Journal Article
de Figueiredo-Pontes, L.L. - Adamcová, Miroslava Kari - Grušanovič, Srdjan - Kuzmina, Maria - Lopes, I. - de Oliveira Costa, A.F. - Zhang, H. - Strnad, Hynek - Lee, S. - Moudra, A. - Jonasova, A.T. - Zidka, M. - Welner, R.S. - Tenen, D.G. - Alberich-Jorda, Meritxell
Improved hematopoietic stem cell transplantation upon inhibition of natural killer cell-derived interferon-gamma.
Stem Cell Reports. Roč. 16, č. 8 (2021), s. 1999-2013. ISSN 2213-6711. E-ISSN 2213-6711
R&D Projects: GA ČR(CZ) GA18-08577S
Institutional support: RVO:68378050
Keywords : t-cells * marrow-transplantation * ifn-gamma * depletion * engraftment * rejection * survival * support * roles
OECD category: Cell biology
Impact factor: 7.294, year: 2021
Method of publishing: Open access
https://linkinghub.elsevier.com/retrieve/pii/S2213671121003143

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 (IFNg) as a potential mediator. Interestingly, improved HSC fitness was achieved by NK cell depletion from murine and human donor infusions or by blocking IFNg 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.
Permanent Link: http://hdl.handle.net/11104/0329628