TNF signalling in rheumatoid arthritis

Tumour necrosis factor (TNF) plays a pivotal role in the mechanism of rheumatoid arthritis. In July Nature Immunology, Hua Wang and colleagues from Genentech Inc., San Francisco, dissected the TNF molecular mechanism and identified new targets for potential therapeutic intervention in autoimmune diseases, such as rheumatoid arthritis, that involve both B and T cells.

Two closely related TNF family ligands, B lymphocyte stimulator (BlyS) and a proliferation-inducing ligand (APRIL), bind to two TNF receptors called transmembrane activator and CAML interactor (TACI) and B cell maturation molecule (BCMA). These ligand-receptor interactions are known to regulate humoral B cell immune responses.

Working with a murine model of rheumatoid arthritis (collagen-induced arthritis -CIA) Wang et al. found that TACI-Fc treatment substantially inhibited inflammation, bone and cartilage destruction and disease development. In addition, TACI-Fc blocked the activation of T cells in vitro and inhibited antigen-specific T cell activation and priming in vivo (Nat Immunol ...