Langford John T, Gonzalez Luis, Taniguchi Ryosuke, Brahmandam Anand, Zhang Weichang, Dardik Alan
Department of Surgery, Yale School of Medicine, New Haven, CT.
Vascular Biology and Therapeutics Program, Yale School of Medicine, New Haven, CT.
JVS Vasc Sci. 2023 May 22;4:100109. doi: 10.1016/j.jvssci.2023.100109. eCollection 2023.
T cells and macrophages play an important role in the formation of allograft vasculopathy, which is the predominant form of chronic rejection in cardiac transplants. Arteries express Ephrin-B2 as a marker of arterial identity, whereas circulating monocytes express the cognate receptor EphB4, which facilitates monocyte adhesion to the endothelial surface. Adherent monocytes transmigrate and differentiate into macrophages that activate T cells and are a main source of tissue damage during rejection. We hypothesized that inhibition of Ephrin-B2-EphB4 binding would decrease immune cell accumulation within a transplanted graft and prevent allograft vasculopathy. We used EphB4 monomer to inhibit Ephrin-B2-EphB4 binding in a rat infrarenal aortic transplant model. Rats treated with EphB4 monomer had fewer macrophages and T cells in the aortic allografts at 28 days, as well as significantly less neointima formation. These data show that the Ephin-B2-EphB4 axis may be an important target for prevention or treatment of allograft vasculopathy.
T细胞和巨噬细胞在同种异体移植血管病变的形成中起重要作用，同种异体移植血管病变是心脏移植中慢性排斥反应的主要形式。动脉表达Ephrin-B2作为动脉特征的标志物，而循环单核细胞表达同源受体EphB4，这有助于单核细胞黏附于内皮表面。黏附的单核细胞迁移并分化为巨噬细胞，巨噬细胞激活T细胞，并且是排斥反应期间组织损伤的主要来源。我们假设抑制Ephrin-B2-EphB4结合会减少移植移植物内免疫细胞的积聚，并预防同种异体移植血管病变。我们在大鼠肾下腹主动脉移植模型中使用EphB4单体来抑制Ephrin-B2-EphB4结合。用EphB4单体治疗的大鼠在28天时主动脉同种异体移植物中的巨噬细胞和T细胞较少，并且新生内膜形成也明显较少。这些数据表明，Ephin-B2-EphB4轴可能是预防或治疗同种异体移植血管病变的重要靶点。
