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

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