Interleukin-12B is upregulated by decoy receptor 3 in rheumatoid synovial fibroblasts

Abstract

Decoy receptor 3 (DcR3) competitively binds to three ligands, Fas ligand, lymphotoxin-related inducible ligand that competes for glycoprotein D binding to herpesvirus entry mediator on T cells and tumor necrosis factor-like ligand 1A (TL1A), to prevent their effects. Recent studies have suggested that DcR3 directly affects cells as a ligand. Using a microarray assay, our group newly identified interleukin (IL)-12B, which encodes the p40 subunit common to IL-12 and IL-23, as one of the genes for which expression in fibroblast-like synoviocytes from patients with rheumatoid arthritis (RA-FLS) is induced by DcR3. The present study demonstrated that IL-12B mRNA expression was upregulated by DcR3-Fc in RA-FLS in a dose-dependent manner, but not in OA-FLS. IL-12B p40 protein in RA-FLS was increased when stimulated with DcR3-Fc. Pre-treatment with anti-TL1A antibody suppressed the upregulation of IL-12B mRNA in RA-FLS stimulated with DcR3-Fc. DcR3 mRNA expression in RA-FLS was induced by IL-23, but not by IL-12. These results indicated that DcR3 may increase IL-12 or IL-23 by inducing IL-12B p40 expression via membrane-bound TL1A on RA-FLS and that IL-23 reciprocally induces DcR3 expression in RA-FLS. DcR3 and IL-23 may interact in a feedback loop that aggravates local inflammation in patients with RA.