Viral 5'-triphosphate RNA and non-CpG DNA aggravate autoimmunity and lupus nephritis via distinct TLR-independent immune responses.
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.
Allam
Ramanjaneyulu
R
Medical Policlinic, University of Munich, Germany.
Pawar
Rahul D
RD
Kulkarni
Onkar P
OP
Hornung
Veit
V
Hartmann
Gunter
G
Segerer
Stephan
S
Akira
Shizuo
S
Endres
Stefan
S
Anders
Hans-Joachim
HJ
D000818:Animals; D001323:Autoantibodies / Q000276:immunology; D015551:Autoimmunity / Q000187:drug effects* / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D018899:CpG Islands; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006942:Hypergammaglobulinemia / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D015850:Interleukin-6 / Q000378:metabolism / Q000494:pharmacology; D008181:Lupus Nephritis / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology; D050527:Mesangial Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D011122:Polyphosphates / Q000737:chemistry*; D012333:RNA, Messenger / Q000235:genetics; D012367:RNA, Viral / Q000737:chemistry* / Q000494:pharmacology*; D013154:Spleen / Q000276:immunology / Q000378:metabolism; D051193:Toll-Like Receptors / Q000276:immunology
D001323:Autoantibodies; D007074:Immunoglobulin G; D015850:Interleukin-6; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D011122:Polyphosphates; D012333:RNA, Messenger; D012367:RNA, Viral; D051193:Toll-Like Receptors; C005692:triphosphoric acid