Departments of Immunobiology and Internal Medicine, Yale University, New Haven, Connecticut, United States of America.
PLoS One. 2012;7(4):e34698. doi: 10.1371/journal.pone.0034698. Epub 2012 Apr 11.
The Receptor for Advanced Glycation Endproducts (RAGE) is a scavenger ligand that binds glycated endproducts as well as molecules released during cell death such as S100b and HMGB1. RAGE is expressed on antigen presenting cells where it may participate in activation of innate immune responses but its role in adaptive human immune responses has not been described. We have found that RAGE is expressed intracellularly in human T cells following TCR activation but constitutively on T cells from patients with diabetes. The levels of RAGE on T cells from patients with diabetes are not related to the level of glucose control. It co-localizes to the endosomes. Its expression increases in activated T cells from healthy control subjects but bystander cells also express RAGE after stimulation of the antigen specific T cells. RAGE ligands enhance RAGE expression. In patients with T1D, the level of RAGE expression decreases with T cell activation. RAGE+ T cells express higher levels of IL-17A, CD107a, and IL-5 than RAGE- cells from the same individual with T1D. Our studies have identified the expression of RAGE on adaptive immune cells and a role for this receptor and its ligands in modulating human immune responses.
晚期糖基化终产物受体（RAGE）是一种清道夫配体，可结合糖化终产物以及细胞死亡过程中释放的分子，如 S100b 和 HMGB1。RAGE 表达于抗原呈递细胞上，可能参与固有免疫反应的激活，但它在适应性人类免疫反应中的作用尚未描述。我们发现，TCR 激活后，人类 T 细胞内会表达 RAGE，但糖尿病患者的 T 细胞则持续表达 RAGE。糖尿病患者 T 细胞上的 RAGE 水平与血糖控制水平无关。它与内体共定位。其在健康对照者激活的 T 细胞中表达增加，但在刺激抗原特异性 T 细胞后，旁观者细胞也表达 RAGE。RAGE 配体增强 RAGE 的表达。在 T1D 患者中，随着 T 细胞的激活，RAGE 的表达水平下降。与 T1D 个体的 RAGE-细胞相比，RAGE+T 细胞表达更高水平的 IL-17A、CD107a 和 IL-5。我们的研究确定了适应性免疫细胞上 RAGE 的表达及其配体在调节人类免疫反应中的作用。
