TNF Superfamily Proteins

TNF family proteins contain a total of 19 TNF ligand family members and their respective receptors. The ligand proteins share the non-covalently linked trimeric extracellular domain. The receptor proteins feature cysteine-rich extracellular domain of varying length. Some ligands share a common receptor and some receptors interact with the same ligand (see above figure). The TNF family proteins govern broad diversity of biology including organizing lymphoid tissues, co-stimulating lymphocyte activation for survival, inducing cell death, bone modeling, skin morphogenesis, as well as regulating neuronal activities. Intensive efforts in these critical biological pathway have led to successful development of numerous key therapeutic biologics including Adalimumab for blocking TNF and treating arthritis, IBD, and uveitis; Belimumab for blocking BAFF, Denosumab for blocking RANKL, both for treating SLE.

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