Hematopoietic cell transplantation (HCT) treats many blood conditions but remains underused due to complications such as graft-versus-host disease (GvHD). In GvHD, donor immune cells attack the patient, requiring powerful immunosuppressive drugs like glucocorticoids (GCs) to prevent death. In this study, we tested the hypothesis that donor cell conditioning with the glucocorticoid fluticasone propionate (FLU) prior to transplantation could increase hematopoietic stem cell (HSC) engraftment and reduce GvHD. Murine HSCs treated with FLU had increased HSC engraftment and reduced severity and incidence of GvHD after transplantation into allogeneic hosts. While most T cells died upon FLU treatment, donor T cells repopulated in the hosts and appeared less inflammatory and alloreactive. Regulatory T cells (Tregs) are immunomodulatory and survived FLU treatment, resulting in an increased ratio of Tregs to conventional T cells. Our results implicate an important role for Tregs in maintaining allogeneic tolerance in FLU-treated grafts and suggest a therapeutic strategy of pre-treating donor cells (and not the patients directly) with GCs to simultaneously enhance engraftment and reduce GvHD upon allogeneic HCT.

中文翻译：

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丙酸氟替卡松的移植物调理可减少小鼠同种异体造血细胞移植后的移植物抗宿主病

造血细胞移植（HCT）可以治疗许多血液疾病，但由于移植物抗宿主病（GvHD）等并发症而仍未得到充分利用。在 GvHD 中，供体免疫细胞攻击患者，需要糖皮质激素 (GC) 等强效免疫抑制药物来防止死亡。在这项研究中，我们测试了这样的假设：移植前用糖皮质激素丙酸氟替卡松 (FLU) 调节供体细胞可以增加造血干细胞 (HSC) 植入并减少 GvHD。移植到同种异体宿主后，用 FLU 处理的小鼠 HSC 增加了 HSC 植入，并降低了 GvHD 的严重程度和发生率。虽然大多数 T 细胞在 FLU 治疗后死亡，但供体 T 细胞在宿主体内重新繁殖，并且炎症和同种反应性减弱。调节性 T 细胞 (Treg) 具有免疫调节作用，在 FLU 治疗后仍能存活，导致 Treg 细胞与传统 T 细胞的比例增加。我们的结果表明Tregs在维持FLU治疗的移植物的同种异体耐受性方面发挥着重要作用，并提出了一种用GC预处理供体细胞（而不是直接治疗患者）的治疗策略，以同时增强植入并减少同种异体HCT后的GvHD。