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.

造血干细胞移植 (HSCT) 是一种常见的治疗方法，用于恢复血液系统疾病患者的造血功能。患者接受富含造血干细胞 (HSC) 的供体细胞输注，还含有免疫细胞，这可能通过消除残留的肿瘤细胞而产生有益效果。然而，供体先天免疫细胞可能对供体 HSC 的影响尚未深入探讨。在这里，我们评估了供体自然杀伤 (NK) 细胞对 HSC 命运的影响，得出结论认为 NK 细胞对 HSC 频率和功能有负面影响，并确定干扰素-γ (IFNγ) 是一种潜在的介质。有趣的是，通过从小鼠和人类供体输液中消耗 NK 细胞或通过阻断 IFNγ 活性来改善 HSC 适应性。因此，