Open AccessThe involvement of Toll‐like receptor 9 in the pathogenesis of erosive autoimmune arthritis
Author(s) -
Fischer Anita,
AbdollahiRoodsaz Shahla,
Böhm Christina,
Niederreiter Birgit,
Meyer Brigitte,
Yau Anthony C. Y.,
Lönnblom Erik,
Joosten Leo A. B.,
Koenders Marije,
Lehmann Christian H. K.,
Dudziak Diana,
Krönke Gerhard,
Holmdahl Rikard,
Steiner Günter
Publication year - 2018
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13735
Subject(s) - tlr9 , arthritis , rheumatoid arthritis , immunology , pathogenesis , inflammatory arthritis , autoimmune disease , rankl , medicine , receptor , synovial fluid , biology , antibody , pathology , gene expression , osteoarthritis , activator (genetics) , biochemistry , alternative medicine , gene , dna methylation
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.