Target Information
TNF alpha is a multifunctional proinflammatory cytokine that belongs to the tumor necrosis factor (TNF) superfamily. This cytokine is mainly secreted by macrophage and bind to its receptors, TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. TNF alpha is involved in the regulation of immune cells, cell proliferation, differentiation, apoptosis, lipid metabolism, and coagulation. TNF alpha exists as a multimer of two, three, or five noncovalently linked units, but shows a single 17 kDa band following SDS-PAGE under non-reducing conditions. Knockout studies in mice also suggested the neuroprotective function of TNF alpha, and has been observed to causes tumor necrosis when injected into tumor-bearing mice. Other functions of TNF-alpha include its role in the immune response to bacterial, viral, parasitic and certain fungal infections, as well as its role in the necrosis of specific tumors. TNF alpha causes cytolysis or cytostasis of certain transformed cells, being synergistic with interferon-gamma in its cytotoxicity. This cytokine has been implicated in a variety of diseases, including autoimmune diseases, insulin resistance, and cancer.
The tumor necrosis factor superfamily member TNFSF4 is a type II membrane bound, non-covalently linked homotrimeric protein. It is expressed on antigen presenting cells, such as dendritic cells and activated B-cells, and also on other cells such as vascular endothelial cells, mast cells, and natural killer cells. TNFSF4 signals specifically through the TNFRSF4 receptor, is expressed predominantly on CD4+T cells but also on certain activated CD8+T cells. TNFRSF4/TNFSF4 functions as a costimulatory signal, which is required for a productive interaction between antigen presenting cells and their target T-cells. It enhances cell proliferation and survival, and increases expression of RANTES, IL-2, IL-3, and IFNgamma. TNFRSF4/TNFSF4 signaling plays an important role in immunotolerance.