Expression of nucleic acid binding Toll-like receptors in control,lupus and transplanted kidneys – a preliminary pilot study

Abstract

We hypothesized that nucleic acids, free and/or complexed, filtered and/or locally released, might be entrapped in the kidneys because of the specific nucleic acid binding microbial pattern recognizing Toll-like receptors (TLRs). This hypothesis of nucleic acid binding potential was tested using paraffin sections from healthy control, SLE and transplant kidneys, which were labelled using TLR-specific rabbit or goat anti–human antibodies in immunoperoxidase staining. Normal and transplant kidneys contain some double- (TLR-3) and single-stranded RNA binding (TLR-8) receptors, but in particular double-stranded RNA binding receptor TLR-7, mostly in tubuli, whereas no DNA binding TLR-9 was found. SLE kidneys contain more TLR-3 and TLR-8 and express de novo also TLR-9, in particular in glomeruli. On the contrary, TLR-7 was relatively weak in SLE. It is concluded that kidneys have a capacity to bind nucleic acids. TLR stimulation leads to the production of tumour necrosis factor-α and other pro-inflammatory cytokines and to up-regulation of co-stimulatory molecules necessary for the adaptive immune response. This makes renal tissues a potential target for inflammatory and immune responses in autoimmune disease and in the reaction for the foreign tissue.