B10 Cells Ameliorate the Progression of Lupus Nephritis by Attenuating Glomerular Endothelial Cell Injury
B10 Cells Ameliorate the Progression of Lupus Nephritis by Attenuating Glomerular Endothelial Cell Injury
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DOI：
10.1159/000430182
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发表时间：
2015-07
影响因子：
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通讯作者：
Miao Yu;Y. Song;Mingxin Zhu;Wei Liang;Qi Long;Pei-wu Ding;Yu Xie;Y. Liao;Jing Yuan
中科院分区：
文献类型：
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作者：
Miao Yu;Y. Song;Mingxin Zhu;Wei Liang;Qi Long;Pei-wu Ding;Yu Xie;Y. Liao;Jing Yuan
背景/目的：B10细胞通常被认为在系统性红斑狼疮（SLE）小鼠模型中具有抑制肾损伤的作用，但最近，由于B细胞中IL-10的谱系特异性缺失，B10细胞的这种功能被否定。因此，本研究旨在确定B10细胞是否以及如何在狼疮性肾炎（LN）中发挥保护作用。方法：收集未接受任何治疗的LN和非LN SLE患者，测定其循环B10细胞百分比。进一步将纯化的B10细胞转移到MRL/lpr SLE小鼠体内，观察B10细胞对LN进展的确切影响。结果如下：患者循环中B10细胞的百分比明显高于健康对照，而LN患者的B10细胞百分比低于非LN SLE患者。此外，B10细胞而不是血浆IL-10水平与LN患者的疾病严重程度，特别是与肾损伤呈负相关。在动物实验中，B10细胞转染的SLE小鼠的肾小球损伤（包括蛋白尿和病理评分）明显减轻，肾小球内皮细胞CD 54/CD 106表达降低，肾小球p38磷酸化和SOCS 3表达增加。同时，B10细胞移植小鼠血清抗dsDNA自身抗体、TNF-α和IFN-γ水平也明显降低，而IL-10和IL-17水平无明显变化。结论：这些结果表明，B10细胞可以通过保护肾小球内皮细胞而非依赖于IL-10来减轻LN肾小球损伤。
Background/Aim: B10 cells are generally considered to inhibit the kidney injury in systemic lupus erythematosus (SLE) mouse models, but recently this function of B10 cells was denied by the lineage-specific deletion of IL-10 from B cells. Thus, this study aimed to determine whether and how B10 cells play a protective role in lupus nephritis (LN). Methods: LN and non-LN SLE patients without receiving any treatments were recruited, and the percentages of circulating B10 cell were determined. Furthermore, the purified B10 cells were transferred into MRL/lpr SLE mice, and the exact effects of B10 cells on LN progression were investigated. Results: The percentage of circulating B10 cells was significantly higher in patient than in healthy controls, while they were fewer in LN patients than non-LN SLE patients. Moreover, B10 cells rather than plasma IL-10 levels were negatively correlated with disease severity especially with kidney injury in LN patients. In animal experiments, the glomerular injuries including the proteinuria and pathological scores were significantly attenuated in SLE mice transferred with B10 cells, accompanied by the decreased glomerular endothelial cell CD54/CD106 expression, and glomerular p38 phosphorylation as well as increased SOCS3 expression. At the same time, the serum anti-dsDNA autoantibody, TNF-α and IFN-γ levels were also reduced, while there were no changes in serum IL-10 and IL-17 levels in B10 cell transferred mice. Conclusion: These findings suggest that B10 cells could - independent from IL-10 - ameliorate glomerular injury in LN through protection of glomerular endothelial cells.