Expression of Toll-like receptor 9 in renal podocytes in childhood-onset active and inactive lupus nephritis
Expression of Toll-like receptor 9 in renal podocytes in childhood-onset active and inactive lupus nephritis
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DOI：
10.1093/ndt/gfq058
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发表时间：
2010-08-01
影响因子：
6.1
通讯作者：
Yokota, Shumpei
中科院分区：
文献类型：
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作者：
Machida, Hiroyuki;Ito, Shuichi;Yokota, Shumpei
背景系统性红斑狼疮（SLE）是儿童期发病的常见疾病，常合并狼疮性肾炎（LN），其特征是肾小球内沉积含DNA的免疫复合物。Toll样受体9（TLR9）能够识别微生物来源的CpG寡核苷酸，在天然免疫中起着重要作用。TLR9也被认为在识别含抗DNA抗体的免疫复合物中与SLE的病因学有关，但这仍然存在争议。我们进行了一项研究，以阐明TLR9和LN在儿童期发病的SLE之间的关联。我们比较了TLR9和狭缝膜相关蛋白的表达和定位在肾活检标本的免疫染色在四个儿童活动性或非活动性LN。我们也评估他们的实验室检查结果，如抗DNA抗体，补体和蛋白尿活检，以评估与免疫染色结果的相关性。结果TLR9在正常对照肾脏中不表达。然而，TLR9仅在活动性LN中在足细胞中产生，但在缓解期消失。与此同时，足细胞中的nephrin、podocin和synaptopodin等狭缝膜相关蛋白在缓解期表达清晰、一致，而在活动期LN中表达明显减少，导致足细胞损伤。当TLR9在足细胞中表达时，所有患者均同时出现低补体血症、高滴度抗双链DNA（dsDNA）抗体和蛋白尿。活动性LN中受损足细胞表达TLR9。这种表达可能与蛋白尿和抗dsDNA抗体升高有关。这是第一个报告表明TLR9参与LN的病因学，它可能在足细胞损伤中发挥一定作用。
Background. Childhood-onset systemic lupus erythematosus (SLE) is frequently complicated with lupus nephritis (LN), which is characterized by the deposition of DNA-containing immune complex to the glomerulus. Toll-like receptor 9 (TLR9), capable of recognizing the microbially derived CpG oligonucleotide, plays a crucial role in the innate immunity. TLR9 is also assumed to be related to the aetiology of SLE in the recognition of anti-DNA antibody-containing immune complex, but this remains controversial. We conducted a study to elucidate the association between TLR9 and LN in childhood-onset SLE.Methods. We compared the expression and localization of TLR9 and the slit membrane-related protein in the biopsied kidney sample by immunostaining in four children with active or inactive LN. We also evaluated their laboratory findings, such as anti-DNA antibody, complement and proteinuria at biopsy, to assess the correlation to the findings of the immunostaining. Results. TLR9 is not expressed in a normal control kidney. However, TLR9 develops in podocytes only in active LN but disappears in remission. Meanwhile, the slit membrane-related proteins such as nephrin, podocin and synaptopodin in podocytes express clearly and uniformly in remission, but their expression is markedly diminished in active LN, which results in podocyte injury. When TLR9 is expressed in podocytes, all the patients simultaneously showed hypocomplementaemia, high titre of anti-double-stranded DNA (dsDNA) antibody and proteinuria.Conclusion. Injured podocytes in active LN express TLR9. This expression could be associated with proteinuria and increased anti-dsDNA antibody. This is the first report indicating that TLR9 is involved in the aetiology of LN and that it may play some role in podocyte injury.