Background Tumor necrosis factor superfamily (TNFSF) and their receptors involve in the pathogenesis of Rheumatoid arthritis (RA) (1).
TNF-like ligand 1A (TL1A), a member of the TNFSF, can be secreted by endothelial cells, dendritic cells, and lymphocytes (2). The receptor for TL1A is death-domain receptor 3 (DR3), which is predominantly expressed on activated lymphocytes (3). TL1A-DR3 signaling can also promote the secretion of IL-17 and regulate the Th17 mediated autoimmune diseases (4).
Decoy receptor 3 (DcR3) belongs to TNF receptor (TNFR) superfamily. DcR3 is a secreted protein which lacks the trans-membrane and cytoplasmic domains. DcR3 can inhibit the function of TL1A-DR3 by compete for the binding of TL1A (5). Therefore, we hypothesized that TL1A-DR3 signaling may be involved in the development of RA by activating Th17 cell function.
Objectives In the present study, we analyzed serum and synovial fluid (SF) levels of TL1A and DcR3 in patients with RA, osteoarthritis (OA) and healthy controls. Moreover, we showed for the first time that TL1A can induce the production of IL-17 by activated peripheral blood mononuclear cells (PBMC) from patients with RA.
Methods The serum and SF levels of TL1A and DcR3, and the production of IL-17 by rhTL1A-treated PBMC were measured by enzyme-linked immunosorbent assay (ELISA). We also tested the change of TL1A and DcR3 level following TNF-α blockade therapy.
Results Serum TL1A and DcR3 levels were higher in RA patients. This increase was more significant in RF and anti-CCP positive patients. TL1A and DcR3 levels were higher in SF samples than in paired sera. TL1A and DcR3 decreased after anti-TNF treatment. rhTL1A increased the production of IL-17.
Conclusions TL1A and DcR3 may be of pathogenic and potentially of therapeutic importance in RA patients.
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Disclosure of Interest None declared
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