Center for Immunity, Inflammation and Regenerative Medicine (CIIR), Division of Nephrology, Department of Medicine, University of Virginia, Charlottesville, VA, USA.
Department of Pathology, Uniformed Services University, Bethesda, MD, USA.
Cell Immunol. 2021 Jun;364:104345. doi: 10.1016/j.cellimm.2021.104345. Epub 2021 Mar 23.
Previously, we generated IL233, a hybrid cytokine composed of interleukin (IL)-2 and IL-33, with better therapeutic potential than either cytokine in multiple inflammatory diseases, in part through promoting T-regulatory cells (Tregs). Here we test the potential of IL233 pretreatment in a murine model of excessive Th1 activation, the parent-into-F1 model of acute GVHD (aGVHD). Five days of IL233 pretreatment of the recipients blocked or delayed the aGVHD-linked loss of B cells as seen in either the peripheral blood (day-11) or lymph nodes (day-14). IL233 pretreatment also prevented the expansion of donor CD8 T-cells in blood and LN at day-14 and significantly reduced day-14 serum IFNγ and TNFα compared to saline treated GVHD mice although, the level of Tregs did not statistically differ between saline and IL233-treated mice. Overall, the current study provides support for the use of IL233 as a therapeutic option in excessive Th1/CD8-driven conditions.
此前，我们生成了一种混合细胞因子 IL233，它由白细胞介素 (IL)-2 和 IL-33 组成，在多种炎症性疾病中的治疗潜力优于这两种细胞因子，部分原因是它能促进 T 调节细胞 (Treg)。在这里，我们在一个过度 Th1 激活的小鼠模型，即急性移植物抗宿主病 (aGVHD) 的亲代到 F1 模型中，测试了 IL233 预处理的潜力。受体接受 5 天的 IL233 预处理可阻止或延迟 aGVHD 导致的外周血（第 11 天）或淋巴结（第 14 天）中 B 细胞的丢失。IL233 预处理还可防止供体 CD8 T 细胞在第 14 天在血液和 LN 中的扩增，并显著降低第 14 天血清 IFNγ 和 TNFα水平，尽管与盐水处理的 GVHD 小鼠相比，Treg 水平在统计学上没有差异。总的来说，本研究为使用 IL233 作为过度 Th1/CD8 驱动条件的治疗选择提供了支持。
