Viral 5'-triphosphate RNA and non-CpG DNA aggravate autoimmunity and lupus nephritis via distinct TLR-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 MRL(lpr/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 MRL(lpr/lpr) mice by specifically activating adaptive immunity but similarly enhance inflammation on the tissue level.

• Authors: Ramanjaneyulu Allam, Rahul D Pawar, Onkar P Kulkarni, Veit Hornung, Gunter Hartmann, Stephan Segerer, Shizuo Akira, Stefan Endres, Hans-Joachim Anders
• Journal: European journal of immunology (Eur J Immunol) Vol. 38 Issue 12 Pg. 3487-98 (Dec 2008) ISSN: 1521-4141 [Electronic] Germany
• PMID: 19009528 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Autoantibodies
• Immunoglobulin G
• Interleukin-6
• Myd88 protein, mouse
• Myeloid Differentiation Factor 88
• Polyphosphates
• RNA, Messenger
• RNA, Viral
• Toll-Like Receptors
• triphosphoric acid

Topics

• Animals
• Autoantibodies (immunology)
• Autoimmunity (drug effects, immunology)
• Cell Proliferation
• Cells, Cultured
• CpG Islands
• Female
• Gene Expression Regulation (drug effects)
• Hypergammaglobulinemia (immunology)
• Immunoglobulin G (immunology)
• Interleukin-6 (metabolism, pharmacology)
• Lupus Nephritis (genetics, immunology, metabolism, pathology)
• Lymphocytes (drug effects, immunology)
• Mesangial Cells (drug effects, immunology, metabolism)
• Mice
• Mice, Knockout
• Myeloid Differentiation Factor 88 (deficiency, genetics, metabolism)
• Polyphosphates (chemistry)
• RNA, Messenger (genetics)
• RNA, Viral (chemistry, pharmacology)
• Spleen (immunology, metabolism)
• Toll-Like Receptors (immunology)