As no previous reports have addressed functional links between TLR4 and IL-12 regulatory axes in the pathogenesis of antibody-induced arthritis, this study provides the first demonstration that TLR4-mediated IL-12 promotes arthritis by regulating the production of both IL-1β and IFN-γ, thereby suppressing TGF-β production. This evidence concerns the gene TLR4 and arthritic joint disease.