Viral 5′-triphosphate RNA and non-CpG DNA aggravate autoimmunity and lupus nephritis via distinctTLR-independent immune responses

Abstract

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. © 2008 Wiley-VCH Verlag GmbH & Co. KGaA.