CD3 mAb treatment ameliorated the severity of the cGVHD-induced lupus nephritis in mice by up-regulation of Foxp3+ regulatory T cells in the target tissue: Kidney
CD3 mAb treatment ameliorated the severity of the cGVHD-induced lupus nephritis in mice by up-regulation of Foxp3+ regulatory T cells in the target tissue: Kidney
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DOI：
10.1016/j.trim.2010.09.002
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发表时间：
2010-10-01
影响因子：
1.5
通讯作者：
Xiao, He
中科院分区：
文献类型：
--
作者：
Zhang, Ji-Lu;Sun, De-Jun;Xiao, He
在DBA/2->；B6D2F1小鼠cGVHD模型中，Teff/Treg失衡导致狼疮性肾炎的发生和发展。在本文中，我们首次使用145-2C11抗体来治疗这些人类SLE样疾病动物。结果表明，短期小剂量抗CD3抗体治疗可显著缓解狼疮性肾病小鼠的蛋白尿、自身抗体产生、免疫复合物沉积和肾实质损害。值得注意的是，我们发现，与对照组相比，抗CD3抗体治疗的小鼠肾脏中Foxp3 mRNA的表达显著上调。同样，在抗CD3抗体处理的小鼠中，也观察到IL-10的肾脏mRNA丰度增加。相反，与炎症和纤维化相关的基因以及与效应性T细胞反应相关的细胞因子在抗CD3单抗治疗后下调。提示短期低剂量抗CD3抗体治疗可在慢性移植物抗宿主病的靶组织肾脏诱导分泌IL-10的Foxp3(+)调节性T细胞，抑制效应T细胞(Th1、Th2和Th17)的激活，从而减轻狼疮性肾炎的严重程度。(C)2010爱思唯尔B.V.保留所有权利。
Teff/Treg imbalance orchestrated the onset and the progression of the lupus nephritis in a DBA/2 -> B6D2F1 murine model with cGVHD. In this paper, we first used 145-2C11 Ab to treat these human SLE-like diseased animals. The results showed that short-term low-dose anti-CD3 antibody treatment induced a significant remission of established proteinuria, production of autoantibodies, immune complex deposition and renal parenchyma lesions in lupus nephritic mice. Of note, we found a robust up-regulation of Foxp3 mRNA expression in the target tissue: kidney from mice with anti-CD3 antibody treatment compared to those with control IgG treatment. Likewise, an increased renal mRNA abundance for IL-10 was also observed in anti-CD3 antibody treated mice. In contrast, genes associated with inflammation and fibrosis as well as cytokines related to effector T cell responses were down-regulated by anti-CD3 mAb treatment. These findings suggested that short-term low-dose anti-CD3 antibody treatment might induced an IL-10-secreting Foxp3(+) regulatory T cells in this cGVHD target tissue: kidney, that suppressed the activation of effector T cells (Th1, Th2 and Th17), thus ameliorating the severity of the lupus nephritis in mice. (C) 2010 Elsevier B.V. All rights reserved.