Department of Liver Transplantation, The Second Xiang-ya Hospital, Central South University, Changsha, Hunan 410011, China; The First Central Clinical School, Tianjin Medical University, Tianjin 300190, China.
Department of Liver Transplantation, The Second Xiang-ya Hospital, Central South University, Changsha, Hunan 410011, China; Transplant Medical Research Center, The Second Xiang-ya Hospital, Central South University, Changsha, Hunan 410011, China.
Int Immunopharmacol. 2023 Aug;121:110407. doi: 10.1016/j.intimp.2023.110407. Epub 2023 Jun 6.
Allograft rejection continues to be a significant cause of morbidity and graft failure for liver transplant recipients. Existing immunosuppressive regimens have many drawbacks, thus safe and effective long-term immunosuppressive regimens are still required. Luteolin (LUT), a natural component found in many plants, has a variety of biological and pharmacological effects and shows good anti-inflammatory activity in inflammatory and autoimmune diseases. Nevertheless, it remains unclear how it affects acute organ rejection after allogeneic transplantation. In this study, a rat liver transplantation model was constructed to investigate the effect of LUT on acute rejection of organ allografts. We found that LUT significantly protected the structure and function of liver grafts, prolonged recipient rat survival, ameliorated T cell infiltration, and downregulated proinflammatory cytokines. Moreover, LUT inhibited the proliferation of CD4 T cells and Th cell differentiation but increased the proportion of Tregs, which is the key to its immunosuppressive effect. In vitro, LUT also significantly inhibited CD4 T cell proliferation and Th1 differentiation. There may be important implications for improving immunosuppressive regimens for organ transplantation as a result of this discovery.
同种异体移植物排斥反应仍然是肝移植受者发病率和移植物失功的重要原因。现有的免疫抑制方案存在许多缺点,因此仍需要安全有效的长期免疫抑制方案。木樨草素(LUT)是一种天然存在于许多植物中的成分,具有多种生物学和药理学作用,并在炎症和自身免疫性疾病中表现出良好的抗炎活性。然而,其对同种异体移植后急性器官排斥的影响尚不清楚。在这项研究中,构建了大鼠肝移植模型,以研究 LUT 对同种异体移植物急性排斥的影响。我们发现 LUT 显著保护了肝移植物的结构和功能,延长了受体大鼠的存活时间,减轻了 T 细胞浸润,并下调了促炎细胞因子。此外,LUT 抑制了 CD4 T 细胞的增殖和 Th 细胞分化,但增加了 Treg 的比例,这是其免疫抑制作用的关键。体外,LUT 还显著抑制了 CD4 T 细胞的增殖和 Th1 分化。这一发现可能对改善器官移植的免疫抑制方案具有重要意义。