2025-04-01 中国科学院(CAS)
<関連情報>
- https://english.cas.cn/newsroom/research_news/life/202503/t20250331_909004.shtml
- https://www.cell.com/cell/abstract/S0092-8674(25)00295-8
急性移植片対宿主病予防における幹細胞注入タイミングの最適化 Optimizing stem cell infusion timing in the prevention of acute graft-versus-host disease
Yiwen Hou∙ Yue Wu∙ Yang Cao∙ … ∙ Dapeng Ju∙ Xiaoyu Zhu∙ Cheng Zhan
Cell Published:March 31, 2025
DOI:https://doi.org/10.1016/j.cell.2025.03.022
Graphical abstract
Highlights
- Early-day stem cell infusions can reduce aGVHD
- The impact of infusion timing depends on the circadian rhythm of recipients
- Prior to infusion, recipient immune milieu differs between early and late day
- Higher IL-1α levels are associated with more severe aGVHD
Summary
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a cornerstone treatment for a broad spectrum of malignant and nonmalignant hematological disorders. However, the success of allo-HSCT is often overshadowed by acute graft-versus-host disease (aGVHD), a life-threatening complication. Here, we show in patients and murine models that the circadian timing of stem cell infusion dictates the development of aGVHD. Early-infused patients exhibit a significantly lower incidence and severity of aGVHD, as well as improved survival. We observed time-of-day variations in the levels of cytokines, especially IL-1α, which controls donor T cell responses after transplantation. The levels of IL-1α in patients were strongly associated with the development of aGVHD. Furthermore, preclinical results showed that the administration of IL-1α neutralizing antibodies markedly alleviated aGVHD and increased survival. Our study suggests that scheduling stem cell infusions early in the day could be a simple yet transformative intervention for preventing aGVHD.
