The role of cytosolic RNA and DNA recognition in systemic autoimmunity and immune complex glomerulonephritis

Ramanjaneyulu, Allam (2010): The role of cytosolic RNA and DNA recognition in systemic autoimmunity and immune complex glomerulonephritis: Cytosoli RNA and DNA recognition in autoimmunity. Dissertation, LMU München: Medizinische Fakultät

Abstract

Non-CpG-DNA and 3P-RNA activated mesangial cells to produce inflammatory cytokines and type 1 interferons in TLR-independent manner. Both ligands induced similar gene expression patterns in mesangial cells. This data unravelled the existence of TLR-independent pathways and production of type1 interferons in mesangial cells. These results substantiate the idea that, immune complexes that are associated with nucleic acids can activate glomerular cells via TLR-independent manner, which leads to glomerular inflammation. Furthermore, exposure of non-CpG-DNA and 3P-RNA in MRLlpr/lpr mice aggravated the disease pathology in different manner. Even though 3P-RNA and non-CpG-DNA induced similar gene expression in mesangial cells but in vivo both ligands aggravated the disease in different fashion. 3P-RNA induced type I IFN signaling and decreased the number of regulatory T cells while non-CpG-DNA induced plasma cell expansion, lymphoproliferation and splenomegaly. However, both ligands induced the production of dsDNA autoantibodies and increased the glomerular deposition of IgG. These data suggest that viral 3P-RNA and non-CpG-DNA differently modulate autoimmunity but still both aggravate autoimmune tissue injury by activating non-immune cells at the tissue level

• Dokumententyp: Dissertationen (Dissertation, LMU München)
• Keywords: Autoimmunity,Lupus, TLRs, Cytosolic DNA, Cytosolic RNA
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften ; 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• Fakultäten: Medizinische Fakultät
• Sprache der Hochschulschrift: Englisch
• Datum der mündlichen Prüfung: 20. Mai 2010
• 1. Bericht­erstatter:in: Anders, Hans-Joachim