Synthetic Double-Stranded RNA Poly(I:C) Aggravates IgA Nephropathy by Triggering IgA Class Switching Recombination through the TLR3-BAFF Axis
Synthetic Double-Stranded RNA Poly(I:C) Aggravates IgA Nephropathy by Triggering IgA Class Switching Recombination through the TLR3-BAFF Axis
复制标题
合成双链 RNA Poly(I:C) 通过 TLR3-BAFF 轴触发 IgA 类别转换重组，从而加重 IgA 肾病
DOI：
10.1159/000440819
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发表时间：
2015
影响因子：
4.2
通讯作者：
Peng Youming
中科院分区：
文献类型：
--
作者：
He Liyu;Peng Xiaofei;Wang Jiayi;Tang Chengyuan;Zhou Xun;Liu Hong;Liu Fuyou;Sun Lin;Peng Youming
背景：免疫球蛋白类开关重组(CSR)对IgA的表达起着至关重要的作用，在IgA肾病(IgAN)的生理病理过程中起着重要作用。本研究旨在探讨聚核苷：多核胞苷酸(Poly(I：C))在调节肿瘤坏死因子家族(BAFF)轴的Toll样受体(TLR)3-B细胞激活因子中的作用，进而促进IgA肾病患者和IgA大鼠模型的IgA CSR。方法：采集24例IgAN患者和26例慢性扁桃体炎患者的血液和扁桃体组织标本。我们还利用IgAN大鼠模型研究了病毒感染与IgA-CSR的关系。结果：免疫组织化学和EL ISA免疫印迹检测显示，与对照组相比，IgA肾病患者TLR3/BAFF轴被激活。合成的双链RNA聚(I：C)刺激上调扁桃体单个核细胞TACI/TLR3/TRIF/TRAF6的表达，促进IgA、CSR和BAFF的产生。TLR3或BAFF siRNA可降低IgA的表达。在IgAN大鼠模型中，TLR3/BAFF信号高度激活。2 0 0μg聚(I：C)钠盐注入左侧鼻孔8周后，免疫球蛋白A在肾小球大量沉积。研究还表明，Poly(I：C)在体内激活了TLR3/BAFF轴和IgA CSR。结论：提示TLR3/BAFF轴在IgA-CSR中的作用，并支持病毒感染黏膜免疫导致黏膜和全身IgA反应受损的观点。
Background: Immunoglobulin class-switch recombination (CSR) is crucial for the expression of IgA, and it plays a vital role in the physiopathology of IgA nephropathy (IgAN). The aim of the study is to investigate the effect of polyriboinosinic:polyribocytidylic acid (poly(I:C)) in modulating toll-like receptor (TLR) 3-B-cell-activating factor belonging to the TNF family (BAFF) axis activation, which in turn promotes IgA CSR of IgAN patients and the IgAN rat model. Methods: Blood samples and tonsillar tissue specimens were obtained from 24 patients with IgAN and 26 patients with chronic tonsillitis as control. We also used the IgAN rat model to investigate the relationship between viral infection and IgA CSR. Results: Immunohistochemical and ELISA western blotting examination revealed that the TLR3/BAFF axis is activated in IgAN patients when compared to controls. Synthetic double-stranded RNA poly(I:C) stimulation upregulates the TACI/TLR3/TRIF/TRAF6 expression and promotes IgA CSR and BAFF productions in tonsil mononuclear cells. TLR3 or BAFF siRNA decreases IgA expression. In IgAN rat models, TLR3/BAFF signaling was highly activated. With 200 μg poly(I:C) sodium salt into the left naris for 8 weeks, IgA was highly deposited on glomeruli. It also revealed that poly(I:C) activated TLR3/BAFF axis and IgA CSR in vivo. Conclusion: These data points toward the role of TLR3/BAFF axis in IgA CSR of IgAN, and the data also support the notion that mucosal immunization with virus infection results in impaired mucosal and systemic IgA responses.