Institute of Pharmacology, University of Bern, Bern, Switzerland.
Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland.
Front Immunol. 2022 Sep 23;13:996746. doi: 10.3389/fimmu.2022.996746. eCollection 2022.
While inhibitory Siglec receptors are known to regulate myeloid cells, less is known about their expression and function in lymphocytes subsets. Here we identified Siglec-7 as a glyco-immune checkpoint expressed on non-exhausted effector memory CD8+ T cells that exhibit high functional and metabolic capacities. Seahorse analysis revealed higher basal respiration and glycolysis levels of Siglec-7 CD8+ T cells in steady state, and particularly upon activation. Siglec-7 polarization into the T cell immune synapse was dependent on sialoglycan interactions and prevented actin polarization and effective T cell responses. Siglec-7 ligands were found to be expressed on both leukemic stem cells and acute myeloid leukemia (AML) cells suggesting the occurrence of glyco-immune checkpoints for Siglec-7 CD8+ T cells, which were found in patients' peripheral blood and bone marrow. Our findings project Siglec-7 as a glyco-immune checkpoint and therapeutic target for T cell-driven disorders and cancer.
虽然抑制性 Siglec 受体已被证实可调节髓系细胞，但关于它们在淋巴细胞亚群中的表达和功能知之甚少。在这里，我们发现 Siglec-7 作为一种糖免疫检查点，表达在非耗竭的效应记忆 CD8+T 细胞上，这些细胞表现出高功能和代谢能力。 Seahorse 分析显示，静止状态下 Siglec-7 CD8+T 细胞的基础呼吸和糖酵解水平较高，特别是在激活后。Siglec-7 在 T 细胞免疫突触中的极化依赖于唾液酸聚糖的相互作用，可防止肌动蛋白极化和有效的 T 细胞反应。发现 Siglec-7 的配体在白血病干细胞和急性髓系白血病 (AML) 细胞上均有表达，这表明 Siglec-7 CD8+T 细胞存在糖免疫检查点，这些检查点存在于患者的外周血和骨髓中。我们的研究结果表明 Siglec-7 是一种糖免疫检查点，也是 T 细胞驱动的疾病和癌症的治疗靶点。
