Abstract：
Glucagon-like peptide-1 receptor (GLP-1R) is a key regulator of glucose metabolism known to be expressed by pancreatic β cells. We herein investigated the role of GLP-1R on T lymphocytes during immune response. Our data showed that a subset of T lymphocytes expresses GLP-1R, which is upregulated during alloimmune response, similarly to PD-1. When mice received islet or cardiac allotransplantation, an expansion of GLP-1Rpos T cells occurred in the spleen and was found to infiltrate the graft. Additional single-cell RNA sequencing (scRNA-seq) analysis conducted on GLP-1Rpos and GLP-1Rneg CD3+ T cells unveiled the existence of molecular and functional dissimilarities between both subpopulations, as the GLP-1Rpos are mainly composed of exhausted CD8 T cells. GLP-1R acts as a T cell-negative costimulatory molecule, and GLP-1R signaling prolongs allograft survival, mitigates alloimmune response, and reduces T lymphocyte graft infiltration. Notably, GLP-1R antagonism triggered anti-tumor immunity when tested in a preclinical mouse model of colorectal cancer.
摘要：
胰高血糖素样肽-1受体(GLP-1R)是已知由胰腺β细胞表达的葡萄糖代谢的关键调节因子。我们在此研究了GLP-1R在免疫应答期间对T淋巴细胞的作用。我们的数据显示，一个T淋巴细胞亚群表达GLP-1R，在同种免疫反应期间上调，类似于PD-1。当小鼠接受胰岛或心脏同种异体移植时，GLP-1RposT细胞在脾脏中扩增,并被发现渗入移植物.对GLP-1Rpos和GLP-1RnegCD3+T细胞进行的其他单细胞RNA测序（scRNA-seq）分析揭示了两个亚群之间存在的分子和功能差异。GLP-1Rpos主要由耗尽的CD8T细胞组成。GLP-1R作为T细胞阴性共刺激分子，和GLP-1R信号延长同种异体移植物存活，减轻同种免疫反应，并减少T淋巴细胞移植物浸润。值得注意的是,当在结肠直肠癌的临床前小鼠模型中测试时,GLP-1R拮抗作用触发抗肿瘤免疫。
