Department of traumatic orthopedics, Shenzhen Longhua District Central Hospital, Shenzhen, China.
Department of Hepatopancreatobiliary Surgery, Shenzhen Institute of Translational Medicine, Health Science Center, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, China.
Front Immunol. 2022 Jun 10;13:853349. doi: 10.3389/fimmu.2022.853349. eCollection 2022.
Islet transplantation to treat the late stage of type 1 diabetic patient (T1DM) has recently made inspiring success in clinical trials. However, most patients experience a decline in islet graft function in one to three years due to immune rejection. Although the mechanisms of immune cells, including macrophages, dendritic cells (DCs), neutrophils, natural killer cells (NKs), B cells, and T cells, that mediate immune rejection have been investigated, the overall characteristics of immune infiltrates in islet allografts and syngeneic grafts remain unclear. Single-cell RNA sequencing (scRNA-seq) has provided us with new opportunities to study the complexity of the immune microenvironment in islet transplants. In the present study, we used scRNA-seq to comprehensively analyze the immune heterogeneity in the mouse model of islet transplantation. Our data revealed T lymphocytes and myeloid cells as the main immune components of grafts 7 days post-islet transplantation, especially in allografts. Moreover, our results indicated that allogeneic islet cells were transformed into antigen-presenting cell-like cells with highly expressed MHC class I molecules and genes involved in MHC class I-mediated antigen presentation. This transformation may dramatically facilitate the interaction with cytotoxic CD8 T cells and promote the destruction of islet allografts. Our study provides insight into the transcriptomics and diverse microenvironment of islet grafts and their impacts on immune rejection.
胰岛移植治疗 1 型糖尿病（T1DM）患者的晚期阶段最近在临床试验中取得了令人鼓舞的成功。然而，由于免疫排斥，大多数患者在 1 至 3 年内经历胰岛移植物功能下降。尽管已经研究了介导免疫排斥的免疫细胞（包括巨噬细胞、树突状细胞（DCs）、中性粒细胞、自然杀伤细胞（NKs）、B 细胞和 T 细胞）的机制，但胰岛同种异体和同基因移植物中免疫浸润的总体特征尚不清楚。单细胞 RNA 测序（scRNA-seq）为我们研究胰岛移植中免疫微环境的复杂性提供了新的机会。在本研究中，我们使用 scRNA-seq 全面分析了胰岛移植小鼠模型中的免疫异质性。我们的数据显示，T 淋巴细胞和髓样细胞是胰岛移植后 7 天移植物的主要免疫成分，特别是在同种异体移植物中。此外，我们的结果表明，同种异体胰岛细胞转化为具有高度表达 MHC Ⅰ类分子和 MHC Ⅰ类介导的抗原呈递相关基因的抗原呈递细胞样细胞。这种转化可能极大地促进了与细胞毒性 CD8 T 细胞的相互作用，并促进了胰岛同种异体移植物的破坏。我们的研究提供了胰岛移植物的转录组学和多样化微环境及其对免疫排斥影响的见解。
