The Ohio State University Comprehensive Cancer Center, Columbus, OH.
Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montréal, Canada; and.
Blood Adv. 2022 Apr 12;6(7):2403-2408. doi: 10.1182/bloodadvances.2021005498.
Acute graft-versus-host disease (aGVHD) is the second most common cause of death after allogeneic hematopoietic stem cell transplantation (allo-HSCT), underscoring the need for novel therapies. Based on previous work that endothelial cell dysfunction is present in aGVHD and that epidermal growth factor-like domain 7 (EGFL7) plays a significant role in decreasing inflammation by repressing endothelial cell activation and T-cell migration, we hypothesized that increasing EGFL7 levels after allo-HSCT will diminish the severity of aGVHD. Here, we show that treatment with recombinant EGFL7 (rEGFL7) in 2 different murine models of aGVHD decreases aGVHD severity and improves survival in recipient mice after allogeneic transplantation with respect to controls without affecting graft-versus-leukemia effect. Furthermore, we showed that rEGFL7 treatment results in higher thymocytes, T, B, and dendritic cell counts in recipient mice after allo-HSCT. This study constitutes a proof of concept of the ability of rEGFL7 therapy to reduce GHVD severity and mortality after allo-HSCT.
急性移植物抗宿主病（aGVHD）是异基因造血干细胞移植（allo-HSCT）后第二大常见死亡原因，这凸显了新型疗法的必要性。基于先前的研究，即内皮细胞功能障碍存在于 aGVHD 中，表皮生长因子样结构域 7（EGFL7）通过抑制内皮细胞激活和 T 细胞迁移来显著发挥抑制炎症的作用，我们假设在 allo-HSCT 后增加 EGFL7 水平将减轻 aGVHD 的严重程度。在这里，我们在 2 种不同的 aGVHD 小鼠模型中表明，重组 EGFL7（rEGFL7）治疗可降低 aGVHD 严重程度，并改善同种异体移植后受体小鼠的存活率，而不会影响移植物抗白血病效应。此外，我们还表明，rEGFL7 治疗可导致同种异体 HSCT 后受体小鼠中的胸腺细胞、T、B 和树突状细胞计数增加。这项研究证明了 rEGFL7 治疗可降低 allo-HSCT 后 aGVHD 的严重程度和死亡率。
