Viral 5′-triphosphate RNA and non-CpG DNA aggravate autoimmunity and lupus nephritis via distinct TLR-independent immune responses
Viral 5′-triphosphate RNA and non-CpG DNA aggravate autoimmunity and lupus nephritis via distinct TLR-independent immune responses
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DOI：
10.1002/eji.200838604
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发表时间：
2008-12-01
影响因子：
5.4
通讯作者：
Anders, Hans-Joachim
中科院分区：
文献类型：
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作者：
Allam, Ramanjaneyulu;Pawar, Rahul D.;Anders, Hans-Joachim
某些病毒核酸通过核酸特异性TLR加重自身免疫。病毒3‘-三磷酸RNA(3P-RNA)和双链非CpG DNA通过TLR非依赖途径诱导抗病毒免疫，但它们在自身免疫中的作用尚不清楚。16wk龄MRLlpr/LPR小鼠短暂暴露于3P-RNA可通过增加干扰素信号和降低CD4(+)CD25(+)T细胞而加重狼疮性肾炎。相比之下，短暂暴露于非CpG DNA可加重狼疮性肾炎，并伴有脾肿大、淋巴组织增生、高丙种球蛋白血症。B220(+)CD138(+)浆细胞增多。与CpG DNA相比，3P-RNA和非CpG DNA均可增加肾小球补体C3c的沉积，但这两种核酸形式在加重肾脏病理方面的作用不如CpG DNA。3P-RNA和非CpG DNA也定位于肾小球系膜细胞，并激活培养的系膜细胞产生IL-6。我们得出结论，3P-RNA或非CpG DNA都通过特异性激活适应性免疫在MRLlpr/LPR小鼠中引发自身免疫性疾病，但类似地在组织水平上增强炎症。
Certain viral nucleic acids aggravate autoimmunity through nucleic acid-specific TLR. Viral 5'-triphosphate RNA (3P-RNA) and double-stranded non-CpG DNA induce antiviral immunity via TLR-independent pathways but their role in autoimmunity is unknown. Transient exposure of 16-wk-old MRLlpr/lpr mice to 3P-RNA aggravated lupus nephritis by increasing IFN signaling and decreasing CD4(+)CD25(+) T cells. By contrast, transient exposure to non-CpG DNA exacerbate lupus nephritis in association with splenomegaly, lymphoproliferation, hypergammaglobulinaemia. and increased B220(+)CD138(+) plasma cells. Both, 3P-RNA and non-CpG DNA increased glomerular complement factor C3c deposits but both nucleic acid formats were less potent in aggravating renal pathology as compared with CpG DNA. 3P-RNA and non-CpG DNA also localized to the glomerular mesangial cells and activated cultured mesangial cells to produce IL-6. We conclude, 3P-RNA or non-CpG DNA both trigger autoimmune disease in MRLlpr/lpr mice by specifically activating adaptive immunity but similarly enhance inflammation on the tissue level.