In a mouse model for rheumatoid arthritis, TNC was responsible for activation of the toll-like receptor-4 (TLR4) pathway in macrophages and fibroblast, leading to the secretion of proinflammatory cytokines, and TNC has been shown to interact with immune cells and play a role in immunomodulatory effects [236]. This evidence concerns the gene TNC and rheumatoid arthritis.