The involvement of Toll-like receptor 9 in the pathogenesis of erosive autoimmune arthritis.
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 TLR9 in the T cell-dependent phase of inflammatory arthritis. In rats with pristane-induced arthritis (PIA), TLR9 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 TLR9-/- 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 TLR7 expression did not change during in vitro osteoclastogenesis, TLR9 expression was higher in precursor cells than in mature osteoclasts and partial inhibition of osteoclastogenesis was achieved only by the TLR9 antagonist. These results demonstrate a pivotal role for TLR9 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.
['Fischer|Anita|A|', 'Abdollahi-Roodsaz|Shahla|S|', 'Böhm|Christina|C|', 'Niederreiter|Birgit|B|', 'Meyer|Brigitte|B|', 'Yau|Anthony C Y|ACY|', 'Lönnblom|Erik|E|', 'Joosten|Leo A B|LAB|', 'Koenders|Marije|M|', 'Lehmann|Christian H K|CHK|', 'Dudziak|Diana|D|', 'Krönke|Gerhard|G|', 'Holmdahl|Rikard|R|', 'Steiner|Günter|G|0000-0002-5089-7405']
D000818:Animals D001169:Arthritis, Experimental D002358:Cartilage, Articular D002473:Cell Wall D045424:Complex Mixtures D005786:Gene Expression Regulation D015850:Interleukin-6 D007596:Joints D051379:Mice D008810:Mice, Inbred C57BL D018345:Mice, Knockout D009961:Orosomucoid D010010:Osteoclasts D010012:Osteogenesis D051381:Rats D012217:Rheumatoid Factor D015398:Signal Transduction D013297:Streptococcus pyogenes D013729:Terpenes D051199:Toll-Like Receptor 7 D051217:Toll-Like Receptor 9
toll-like receptor arthritis bone erosion osteoclastogenesis inflammation