Expression of the novel co-stimulatory molecule B7-H4 by renal tubular epithelial cells
Expression of the novel co-stimulatory molecule B7-H4 by renal tubular epithelial cells
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DOI：
10.1038/sj.ki.5001867
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发表时间：
2006-12-01
影响因子：
19.6
通讯作者：
Wu, Y.
中科院分区：
文献类型：
--
作者：
Chen, Y.;Yang, C.;Wu, Y.
肾小管病变是进行性肾脏疾病的最重要标志，其发病机制中T细胞和肾小管上皮细胞（TEC）之间的相互作用尚未阐明。先前的研究表明，TEC具有促进T细胞活化的共刺激信号，这诱导了肾小管病变。然而，B7-H4，一个最近发现的B7超家族的共刺激配体，在病理人类肾脏中的表达和功能作用尚不清楚。我们采用免疫组织化学方法研究了20例特发性膜性肾病、19例免疫球蛋白A肾病、16例狼疮性肾炎和15例急性肾移植排斥反应患者的冷冻肾活检组织中B7-H4的表达。此外，我们还分析了TEC相关的B7-H4在调节T细胞活化中的作用。免疫组织化学染色显示，B7-H4抗原仅限于肾小管上皮细胞，蛋白质是突出的部分与严重的肾小管病变，虽然没有相关性之间观察到肾小管B7-H4表达和血清肌酐水平，血清尿素氮浓度，24小时蛋白尿在每种类型的肾病。在体外，混合淋巴细胞反应表明，TEC相关的B7-H4促进细胞因子（白细胞介素-2和干扰素-γ）的生产和共培养的T细胞的增殖。有趣的是，当C10细胞与B7-H4转基因鼠TEC系、3 M-1分泌性肾小管上皮细胞（MCT）在抗原鸡蛋溶菌酶存在下共培养时，C10 T细胞杂交瘤的白细胞介素-2分泌也增加。我们的研究结果清楚地表明，TEC相关的B7-H4诱导T细胞活化，我们建议，B7-H4是一个潜在的激活剂，促进肾小管病变。
Crosstalk between T cells and renal tubular epithelial cells (TECs) in the pathogenesis of tubular lesions, the most important sign of progressive renal diseases, has not been clarified. Previous work has shown that TECs harbor co-stimulatory signals that promote T-cell activation, which induces tubular lesions. Nevertheless, the expression and functional role of B7-H4, a recently identified co-stimulatory ligand of the B7 superfamily, in pathologic human kidneys is unclear. We investigated the expression of B7-H4 on cryostat renal biopsies from patients with idiopathic membranous nephropathy (n=20), immunoglobulin A nephropathy (n=19), lupus nephritis (n=16), and acute renal allograft rejection (n=15) using immunohistochemistry. In addition, we also analyzed TEC-associated B7-H4 in the regulation of T-cell activation. Immunohistological staining revealed that B7-H4 antigen is restricted to tubular epithelium and that the protein is prominent in sections with severe tubular lesions, although no correlation was observed between tubular B7-H4 expression and levels of serum creatinine, serum urea nitrogen concentration, and 24-h proteinuria in each type of nephropathy. In vitro, mixed lymphocyte reactions revealed that TEC-related B7-H4 promotes cytokine (interleukin-2 and interferon-gamma) production and proliferation of co-cultured T cells. Interestingly, the secretion of interleukin-2 by C10 T cell hybridomas also increased when C10 cells were co-cultured with the B7-H4-transgenic murine TEC line, 3M-1-secreting tubular epithelial cells (MCT) in the presence of the antigen hen egg lysozyme. Our results clearly show that TEC-associated B7-H4 induces T-cell activation and we propose that B7-H4 is a potential activator that promotes tubular lesion.