Department of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Road, Shanghai 200025, China.
Front Biosci (Landmark Ed). 2012 Jan 1;17(5):1795-803. doi: 10.2741/4019.
The role of DC-SIGN in tubulointerstitial lesions (TILs) and the effect of anti-P-selectin lectin-EGF domain monoclonal antibody (PsL-EGFmAb) were investigated in rat nephrotoxic nephritis (NTN). On Day 4, immature DC-SIGN+DCs infiltrated into renal tubulointerstitium and matured by Day 14, showing increased migratory capacity and ability to induce T cell proliferation. The distribution of DC-SIGN+ DC significantly correlated with crescent formation, TIL severity, and changes in renal function. RANTES and TNF-alpha mRNA were continuously up-regulated from Day 4, while IL-10 mRNA was down-regulated after a marked increase on Day 4. Expression of IFN-gamma and IL-4 mRNA increased on Day 14 due to DC maturation. PsL-EGFmAb suppressed DC maturation, migration and ability to activate T cells. It also down-regulated TNF-alpha and up-regulated IL-10, resulting in a Th1/Th2 bias. The number of crescents decreased and TILs and renal function improved. These results suggest that DC-SIGN mediates DC tubulointerstitial infiltration and is an important regulator of local immune reactions and TILs. PsL-EGFmAb inhibited DC migration, maturation and function by targeting DC-SIGN, and may therefore be a potential treatment for NTN.
探讨树突状细胞（DC）特异性细胞间黏附分子-3 结合非整合素（DC-SIGN）在大鼠抗肾小球基底膜肾炎（抗 GBM 肾炎）肾间质病变（TIL）中的作用，以及抗 P 选择素糖蛋白配体-表皮生长因子结构域单克隆抗体（PsL-EGFmAb）的作用。
抗 GBM 肾炎大鼠模型第 4 天，不成熟 DC-SIGN+DC 浸润到肾小管间质，第 14 天成熟，表现为迁移能力和诱导 T 细胞增殖能力增强。DC-SIGN+DC 的分布与新月体形成、TIL 严重程度和肾功能变化显著相关。RANTES 和 TNF-αmRNA 从第 4 天持续上调，而 IL-10mRNA 在第 4 天明显增加后下调。第 14 天，由于 DC 成熟，IFN-γ和 IL-4mRNA 的表达增加。PsL-EGFmAb 抑制 DC 成熟、迁移和激活 T 细胞的能力。它还下调 TNF-α，上调 IL-10，导致 Th1/Th2 失衡。新月体数量减少，TIL 和肾功能改善。
DC-SIGN 介导 DC 向肾小管间质浸润，是局部免疫反应和 TIL 的重要调节因子。PsL-EGFmAb 通过靶向 DC-SIGN 抑制 DC 迁移、成熟和功能，可能是抗 GBM 肾炎的一种潜在治疗方法。
