The involvement of Toll‐like receptor 9 in the pathogenesis of erosive autoimmune arthritis

Abstract

Abstract Endogenous nucleic acids and their receptors may be involved in the initiation of systemic autoimmune diseases including rheumatoid arthritis ( RA ). As the role of the DNA sensing Toll‐like receptor ( TLR ) 9 in RA is unclear, we aimed to investigate its involvement in the pathogenesis of autoimmune arthritis using three different experimental models of RA . The data obtained revealed involvement of TLR 9 in the T cell‐dependent phase of inflammatory arthritis. In rats with pristane‐induced arthritis ( PIA ), TLR 9 inhibition before disease onset reduced arthritis significantly and almost completely abolished bone erosion. Accordingly, serum levels of IL ‐6, α‐1‐acid‐glycoprotein and rheumatoid factor were reduced. Moreover, in TLR 9 −/− mice, streptococcal cell wall (SCW)‐induced arthritis was reduced in the T cell‐dependent phase, whereas T cell‐independent serum‐transfer arthritis was not affected. Remarkably, while TLR 7 expression did not change during in vitro osteoclastogenesis, TLR 9 expression was higher in precursor cells than in mature osteoclasts and partial inhibition of osteoclastogenesis was achieved only by the TLR 9 antagonist. These results demonstrate a pivotal role for TLR 9 in the T cell‐dependent phases of inflammatory arthritis and additionally suggest some role during osteoclastogenesis. Hence, endogenous DNA seems to be crucially involved in the pathophysiology of inflammatory autoimmune arthritis.