Department of Emergency and Organ Transplantation, Nephrology, Dialysis, and Transplantation Unit, University of Bari, Italy.
Kidney Int. 2011 Jun;79(11):1228-35. doi: 10.1038/ki.2011.32. Epub 2011 Feb 23.
Dendritic cells (DCs) have a pivotal role in the autoimmune response of systemic lupus erythematosus. Plasmacytoid DCs infiltrate the kidney of patients with lupus nephritis, but factors regulating their recruitment to the kidney are unknown. Chemerin is the recently identified natural ligand of ChemR23, a receptor highly expressed by plasmacytoid DCs. We performed immunohistochemical and immunofluorescence analysis to study the ChemR23/Chemerin axis in renal biopsies from patients with lupus nephritis. We found ChemR23-positive DCs had infiltrated the kidney tubulointerstitium in patients with severe lupus nephritis. Chemerin association with tubular epithelial cells and renal lymphatic endothelial cells was found in patients with lupus nephritis but not in normal kidneys. Proximal tubular epithelial cells produced Chemerin in vitro, which was significantly down-modulated by added tumor necrosis factor (TNF)-α and interferon-γ as measured by quantitative PCR and enzyme-linked immunosorbent assay. Interestingly, TNF-α was capable of inducing a functionally active form of renal Chemerin, resulting in an efficient transendothelial migration of plasmacytoid DCs measured in transwell systems. Thus, the ChemR23/Chemerin axis may have a role in the recruitment of DCs within the kidney in patients affected by lupus nephritis.
树突状细胞 (DCs) 在系统性红斑狼疮的自身免疫反应中具有关键作用。浆细胞样 DCs 浸润狼疮肾炎患者的肾脏，但调节其向肾脏募集的因素尚不清楚。趋化素是 ChemR23 的天然配体，ChemR23 是浆细胞样 DCs 高度表达的受体。我们进行了免疫组织化学和免疫荧光分析，以研究狼疮肾炎患者肾活检中的 ChemR23/趋化素轴。我们发现，在严重狼疮肾炎患者中，ChemR23 阳性 DCs 已浸润到肾小管间质中。在狼疮肾炎患者中发现 Chemerin 与肾小管上皮细胞和肾淋巴管内皮细胞有关，但在正常肾脏中没有发现。体外培养的近端肾小管上皮细胞产生 Chemerin，定量 PCR 和酶联免疫吸附试验显示，添加肿瘤坏死因子 (TNF)-α 和干扰素-γ 可显著下调 Chemerin。有趣的是，TNF-α 能够诱导肾 Chemerin 的功能性活性形式，导致在 Transwell 系统中测量的浆细胞样 DCs 的跨内皮迁移效率提高。因此，ChemR23/趋化素轴可能在狼疮肾炎患者肾脏内 DCs 的募集中发挥作用。
