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.