Department of Pathology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX, 75390-9072, USA.
Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
Sci Rep. 2024 Mar 19;14(1):6625. doi: 10.1038/s41598-024-57162-3.
The role of glycan-binding proteins as an activator of immune regulatory receptors has gained attention recently. We report that galectin 7 reduced CD4+ T cell percentage in both in vitro culture and mouse tumor models. Immunohistochemical staining of esophageal cancer patient samples showed a lower percentage of CD4+ cells in the galectin 7 high area. The lack of CD4+ T cell depletion by galectin 7 in PD-1 knockout mice supports the role of PD-1 in mediating the effects of galectin 7. The binding assays demonstrate that galectin 7 binds to the N-glycosylation of PD-1 on N74 and N116 sites and leads to the recruitment of SHP-2. NFAT suppressive activity of galectin 7 was abrogated upon overexpression of the dominant negative SHP-2 mutant or inhibition of PD-1 by siRNA. Glycosylation of PD-1 has been reported to play a critical role in surface expression, stability, and interaction with its ligand PD-L1. This report further expands the significance of PD-1 glycosylation and suggests that galectin 7, a glycan-binding protein, interacts with the immune regulatory receptor PD-1 through glycosylation recognition.
糖结合蛋白作为免疫调节受体的激活剂的作用最近引起了关注。我们报告称，半乳糖凝集素 7 在体外培养和小鼠肿瘤模型中均降低了 CD4+T 细胞的比例。食管癌患者样本的免疫组织化学染色显示，半乳糖凝集素 7 高表达区域的 CD4+T 细胞比例较低。在 PD-1 敲除小鼠中，半乳糖凝集素 7 缺乏对 CD4+T 细胞的耗竭作用支持 PD-1 在介导半乳糖凝集素 7 作用中的作用。结合实验表明，半乳糖凝集素 7 与 PD-1 上 N74 和 N116 位点的 N-糖基化结合，并导致 SHP-2 的募集。半乳糖凝集素 7 的 NFAT 抑制活性在过表达显性负 SHP-2 突变体或通过 siRNA 抑制 PD-1 时被阻断。PD-1 的糖基化已被报道在表面表达、稳定性和与其配体 PD-L1 的相互作用中起关键作用。本报告进一步扩展了 PD-1 糖基化的意义，并表明糖结合蛋白半乳糖凝集素 7 通过糖基化识别与免疫调节受体 PD-1 相互作用。
