The possible role of ChemR23/chemerin axis in the recruitment of dendritic cells in lupus nephritis
The possible role of ChemR23/chemerin axis in the recruitment of dendritic cells in lupus nephritis
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DOI：
10.1038/ki.2011.32
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发表时间：
2011-06-01
影响因子：
19.6
通讯作者：
Schena, Francesco P.
中科院分区：
文献类型：
--
作者：
De Palma, Giuseppe;Castellano, Giuseppe;Schena, Francesco P.
树突状细胞（Dendritic cells，DCs）在系统性红斑狼疮（SLE）的自身免疫反应中起关键作用。浆细胞样树突状细胞浸润狼疮肾炎患者的肾脏，但调节其募集到肾脏的因素尚不清楚。Chemerin是最近鉴定的ChemR 23的天然配体，ChemR 23是由浆细胞样DC高度表达的受体。我们进行免疫组织化学和免疫荧光分析，以研究狼疮性肾炎患者肾活检中的ChemR 23/chemerin轴。我们发现在重症狼疮性肾炎患者中，ChemR 23阳性DC已浸润肾小管上皮细胞。在狼疮性肾炎患者中发现Chemerin与肾小管上皮细胞和肾淋巴管内皮细胞结合，而在正常肾脏中未发现Chemerin。近端肾小管上皮细胞产生chemerin在体外，这是显着下调添加肿瘤坏死因子（TNF）-α和干扰素-γ通过定量PCR和酶联免疫吸附测定。有趣的是，TNF-α能够诱导肾趋化蛋白的功能活性形式，导致在transwell系统中测量的浆细胞样DC的有效跨内皮迁移。因此，ChemR 23/chemerin轴可能在狼疮性肾炎患者肾脏内DC的募集中起作用。Kidney International（2011）79，1228-1235; doi：10.1038/ki.2011.32; 2011年2月23日在线发表
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)-alpha and interferon-gamma as measured by quantitative PCR and enzyme-linked immunosorbent assay. Interestingly, TNF-alpha 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. Kidney International (2011) 79, 1228-1235; doi:10.1038/ki.2011.32; published online 23 February 2011