Toll-like receptor 3 expression and function in childhood idiopathic nephrotic syndrome
Toll-like receptor 3 expression and function in childhood idiopathic nephrotic syndrome
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DOI：
10.1111/cei.12659
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发表时间：
2015-12-01
影响因子：
4.6
通讯作者：
Deschenes, G.
中科院分区：
文献类型：
--
作者：
Jamin, A.;Dehoux, L.;Deschenes, G.
类固醇和免疫抑制治疗对特发性肾病综合征（INS）的疗效暗示了免疫细胞在该疾病的病理生理学中的作用。Toll样受体（TLR）功能障碍与多种免疫源性肾脏疾病有关，但在INS中的研究较少。我们研究了28例复发、23例缓解和40例对照INS患儿外周血单个核细胞（PBMC）中TLR的表达和功能。没有儿童有任何感染的迹象，但在复发患者的PBMC中测量到更高的EB病毒病毒载量。TLR-3的表达仅在INS缓解期间在B细胞中增加。INS患者蛋白尿与外周血单个核细胞TLR-3表达呈负相关。在INS缓解期，TLR-8在CD 4（+）T细胞和B细胞中的表达也增加。INS患者蛋白尿与总PBMC、CD 4 + T细胞和B细胞TLR-8表达呈负相关。然而，在另一组15名INS患者中，TLR-3和TLR-8的表达在利妥昔单抗治疗后B细胞补充缓解的所有PBMC亚群中均正常化。特别是，所有INS患者PBMC中的干扰素（IFN）调节因子3反式激活增加。在体外分泌的IFN-和白细胞介素6的INS缓解患者的PBMC中自发增加，而从所有INS患者的PBMC显示TLR-3刺激后IFN-分泌受损。因此，TLR-3通路功能障碍可能与INS发病机制密切相关。
The efficacy of steroids and immunosuppressive treatments in idiopathic nephrotic syndrome (INS) hints at the implication of immune cells in the pathophysiology of the disease. Toll-like receptor (TLR) dysfunctions are involved in many kidney diseases of immune origin, but remain little described in INS. We investigated the expression and function of TLRs in peripheral blood mononuclear cells (PBMC) of INS children, including 28 in relapse, 23 in remission and 40 controls. No child had any sign of infection, but a higher Epstein-Barr virus viral load was measured in the PBMC of relapsing patients. TLR-3 expression was increased in B cells only during INS remission. There was a negative correlation between proteinuria and TLR-3 expression in total and the main subsets of PBMC from INS patients. The expression of TLR-8 was also increased in both CD4(+) T cells and B cells in INS remission. There was a negative correlation between proteinuria and TLR-8 expression in total PBMC, CD4(+) T cells and B cells of INS patients. Nevertheless, TLR-3 and TLR-8 expression was normalized in all PBMC subsets in an additional group of 15 INS patients in remission with B cell repletion after rituximab therapy. Paradoxically, interferon (IFN) regulatory factor 3 transactivation was increased in PBMC of all INS patients. In-vitro secretion of IFN- and interleukin 6 were increased spontaneously in PBMC of INS remission patients, whereas PBMC from all INS patients displayed an impaired IFN- secretion after TLR-3 stimulation. Thus, TLR-3 pathway dysfunctions may be closely involved in INS pathogenesis.