Department of Anesthesiology, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
Center for Translational Medicine, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
Sci Transl Med. 2021 Feb 3;13(579). doi: 10.1126/scitranslmed.abb6576.
Eosinophils are a myeloid cell subpopulation that mediates type 2 T helper cell immune responses. Unexpectedly, we identified a rapid accumulation of eosinophils in 22 human liver grafts after hepatic transplantation. In contrast, no eosinophils were detectable in healthy liver tissues before transplantation. Studies with two genetic mouse models of eosinophil deficiency and a mouse model of antibody-mediated eosinophil depletion revealed exacerbated liver injury after hepatic ischemia and reperfusion. Adoptive transfer of bone marrow-derived eosinophils normalized liver injury of eosinophil-deficient mice and reduced hepatic ischemia and reperfusion injury in wild-type mice. Mechanistic studies combining genetic and adoptive transfer approaches identified a critical role of suppression of tumorigenicity (ST2)-dependent production of interleukin-13 by eosinophils in the hepatoprotection against ischemia-reperfusion-induced injury. Together, these data provide insight into a mechanism of eosinophil-mediated liver protection that could serve as a therapeutic target to improve outcomes of patients undergoing liver transplantation.
嗜酸性粒细胞是一种髓系细胞亚群，可介导 2 型 T 辅助细胞免疫应答。出乎意料的是，我们在肝移植后 22 个人类肝移植物中发现了嗜酸性粒细胞的快速积累。相比之下，在移植前的健康肝组织中无法检测到嗜酸性粒细胞。通过对两种嗜酸性粒细胞缺乏的遗传小鼠模型和一种抗体介导的嗜酸性粒细胞耗竭的小鼠模型进行研究，发现在肝缺血再灌注后肝损伤加剧。骨髓来源的嗜酸性粒细胞过继转移可使嗜酸性粒细胞缺乏的小鼠的肝损伤正常化，并降低野生型小鼠的肝缺血再灌注损伤。结合遗传和过继转移方法的机制研究表明，嗜酸性粒细胞抑制肿瘤发生（ST2）依赖性产生白细胞介素-13 在对抗缺血再灌注诱导损伤的肝保护中起关键作用。总之，这些数据提供了对嗜酸性粒细胞介导的肝保护机制的深入了解，可作为改善肝移植患者预后的治疗靶点。
