Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan; Institute of Molecular Medicine, Feinstein Institutes for Medical Research, Manhasset, NY, USA.
Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Clin Immunol. 2023 May;250:109317. doi: 10.1016/j.clim.2023.109317. Epub 2023 Apr 2.
The receptor for advanced glycation end-products (RAGE) is a pattern recognition receptor that regulates inflammation, cell migration, and cell fate. Systemic lupus erythematosus (SLE) is a chronic multiorgan autoimmune disease. To understand the function of RAGE in SLE, we generated RAGE-deficient (Ager) lupus-prone mice by backcrossing MRL/MpJ-Fas/J (MRL-lpr) mice with Ager C57BL/6 mice. In 18-week-old Ager MRL-lpr, the weights of the spleen and lymph nodes, as well as the frequency of CD3CD4CD8 cells, were significantly decreased. Ager MRL-lpr mice had significantly reduced urine albumin/creatinine ratios and markedly improved renal pathological scores. Moreover, neutrophil infiltration and neutrophil extracellular trap formation in the glomerulus were significantly reduced in Ager MRL-lpr. Our study is the first to reveal that RAGE can have a pathologic role in immune cells, particularly neutrophils and T cells, in inflammatory tissues and suggests that the inhibition of RAGE may be a potential therapeutic strategy for SLE.
晚期糖基化终产物受体（RAGE）是一种模式识别受体，可调节炎症、细胞迁移和细胞命运。系统性红斑狼疮（SLE）是一种慢性多器官自身免疫性疾病。为了了解 RAGE 在 SLE 中的功能，我们通过将 MRL/MpJ-Fas/J（MRL-lpr）小鼠与 Ager C57BL/6 小鼠回交，生成了 RAGE 缺陷（Ager）狼疮易感小鼠。在 18 周龄的 Ager MRL-lpr 中，脾脏和淋巴结的重量以及 CD3CD4CD8 细胞的频率显著降低。Ager MRL-lpr 小鼠的尿白蛋白/肌酐比值显著降低，肾脏病理评分明显改善。此外，Ager MRL-lpr 肾小球中的中性粒细胞浸润和中性粒细胞胞外陷阱形成明显减少。我们的研究首次揭示 RAGE 可在炎症组织中的免疫细胞（尤其是中性粒细胞和 T 细胞）中发挥病理作用，并表明抑制 RAGE 可能是 SLE 的一种潜在治疗策略。
