Liver Transplantation Center, National Clinical Research Center for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
Clinical Research Center for Pediatric Liver Transplantation, Capital Medical University, Beijing, China.
Front Immunol. 2022 Jul 28;13:953240. doi: 10.3389/fimmu.2022.953240. eCollection 2022.
Accumulating evidence indicates the critical roles of group 2 innate lymphoid cells (ILC2s) in immunoregulation. However, the role of ILC2s in acute rejection after liver transplantation (LT) remains elusive. In this study, we analyzed the frequency, counts, and signature cytokines of ILC2s in liver transplant recipients by flow cytometric analysis and multiplex immunofluorescence assay. We also assessed the spatial distribution and correlation between hepatic ILC2s and Treg cells. The changes of ILC2s were dynamically monitored in the mouse LT model. We found that the frequencies of circulating ILC2s were comparable in liver transplant recipients with either rejection or non-rejection compared with the control group. The hepatic ILC2s counts were significantly increased in the rejection group than in the non-rejection and control groups, and a similar trend was observed for Treg cells. In the mouse LT model, allograft infiltrating ILC2s dramatically increased within 14 days post-transplant. The frequency of ILC2s in bone marrow significantly increased at 7 days post-transplant and rapidly decreased at 14 days after LT. Similarly, there was a significant increase in the frequency of splenic ILC2s within two weeks post-transplant. Multiplex immunofluorescence assay showed a close correlation between hepatic ILC2s and Treg cells by analyzing their spatial distribution and distance. In conclusion, the number of allograft infiltrating ILC2s was closely related to rejection after LT. Allograft infiltrating ILC2s may play inhibitory roles in posttransplant immune homeostasis, favoring resolution of liver allograft rejection by interacting with Treg cells or promoting the migration of Tregs cells into the liver allograft.
越来越多的证据表明，2 型固有淋巴细胞（ILC2）在免疫调节中起着关键作用。然而，ILC2 在肝移植（LT）后急性排斥反应中的作用仍不清楚。在这项研究中，我们通过流式细胞术分析和多重免疫荧光检测分析了肝移植受者 ILC2 的频率、计数和特征细胞因子。我们还评估了肝内 ILC2 与 Treg 细胞之间的空间分布和相关性。在小鼠 LT 模型中动态监测 ILC2 的变化。我们发现，与对照组相比，排斥组和非排斥组的循环 ILC2 频率相似。排斥组的肝内 ILC2 计数明显高于非排斥组和对照组，Treg 细胞也有类似的趋势。在小鼠 LT 模型中，同种异体移植物浸润的 ILC2 在移植后 14 天内急剧增加。骨髓中 ILC2 的频率在移植后 7 天明显增加，在 LT 后 14 天迅速下降。同样，移植后两周内脾内 ILC2 的频率也显著增加。通过分析肝内 ILC2 和 Treg 细胞的空间分布和距离，多重免疫荧光检测显示它们之间存在密切相关性。总之，同种异体移植物浸润的 ILC2 数量与 LT 后的排斥反应密切相关。同种异体移植物浸润的 ILC2 可能通过与 Treg 细胞相互作用或促进 Treg 细胞向肝移植移植物迁移，在移植后免疫稳态中发挥抑制作用，有利于肝脏移植物排斥反应的消退。
