The importance of PD-1/PD-L1 interaction to alloimmune response is unknown in intestinal transplantation. We tested whether PD-L1 regulates allograft tissue injury in murine intestinal transplantation. PD-L1 expression was observed on the endothelium and immune cells in the intestinal allograft. Monoclonal antibody treatment against PD-L1 led to accelerated allograft tissue damage, characterized by severe cellular infiltrations, massive destruction of villi, and increased crypt apoptosis in the graft. Interestingly, PD-L1^−/− allografts were more severely rejected than wild-type allografts, but the presence or absence of PD-L1 in recipients did not affect the degree of allograft injury. PD-L1^−/− allografts showed increased infiltrating Ly6G⁺ and CD11b⁺ cells in lamina propria on day 4, whereas the degree of CD4⁺ or CD8⁺ T cell infiltration was comparable to wild-type allografts. Gene expression analysis revealed that PD-L1^−/− allografts had increased mRNA expressions of Cxcr2, S100a8/9, Nox1, IL1rL1, IL1r2, and Nos2 in the lamina propria cells on day 4. Taken together, study results suggest that PD-L1 expression in the intestinal allograft, but not in the recipient, plays a critical role in mitigating allograft tissue damage in the early phase after transplantation. The PD-1/PD-L1 interaction may contribute to immune regulation of the intestinal allograft via the innate immune system.

中文翻译：

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阻断或缺乏肠同种异体移植物中的 PD-L1 表达会加速小鼠移植物组织损伤

PD-1/PD-L1 相互作用对同种免疫反应的重要性在肠移植中尚不清楚。我们测试了 PD-L1 是否调节小鼠肠道移植中的同种异体移植组织损伤。在同种异体肠移植物的内皮细胞和免疫细胞上观察到 PD-L1 表达。针对 PD-L1 的单克隆抗体治疗导致同种异体移植物组织损伤加速，其特征是严重的细胞浸润、绒毛的大量破坏和移植物中隐窝细胞凋亡的增加。有趣的是，PD-L1 ^-/-同种异体移植物比野生型同种异体移植物被更严重地排斥，但受体中是否存在 PD-L1 并不影响同种异体移植物损伤的程度。PD-L1 ^-/-同种异体移植物显示浸润性 Ly6G ⁺和 CD11b增加⁺细胞在第 4 天在固有层中，而 CD4 ⁺或 CD8 ⁺ T 细胞浸润的程度与野生型同种异体移植物相当。基因表达分析表明，PD-L1 ^-/-同种异体移植物增加了Cxcr2、S100a8 / 9、Nox1、IL1rL1、IL1r2和Nos2的 mRNA 表达第 4 天在固有层细胞中。综上所述，研究结果表明，PD-L1 在同种异体肠移植物中的表达，而不是在受体中的表达，在移植后早期减轻同种异体移植物组织损伤方面起着关键作用。PD-1/PD-L1 相互作用可能通过先天免疫系统促进肠道同种异体移植物的免疫调节。