Tumor necrosis factor receptor 2

Tumor Necrosis Factor Receptor 2 (TNFR2) is a protein that in humans is encoded by the TNFRSF1B gene. It is one of the receptors for tumor necrosis factor (TNF), a major cytokine involved in systemic inflammation and the stimulation of the acute phase response. TNFR2 is expressed in a variety of human tissues, including cells of the immune system, neurons, and endothelial cells. This receptor plays a significant role in the regulation of the immune response, cell proliferation, apoptosis, and inflammation.

Structure and Function

TNFR2 is a type I membrane protein that belongs to the TNF receptor superfamily. It is characterized by the presence of cysteine-rich domains in its extracellular region, which are essential for its binding to TNF. Unlike TNFR1, TNFR2 does not contain a death domain in its intracellular region, which means it generally activates survival pathways rather than apoptotic pathways. TNFR2 can be activated by both the membrane-bound form and the soluble form of TNF, although it has a higher affinity for the membrane-bound form of TNF.

Upon activation by its ligand, TNFR2 initiates several signaling pathways, including the activation of NF-κB and MAPK pathways. These pathways lead to the expression of genes involved in cell survival, proliferation, and inflammation. TNFR2 signaling is also involved in the activation and expansion of regulatory T cells (Tregs), which play a crucial role in maintaining immune tolerance and preventing autoimmune responses.

Clinical Significance

The role of TNFR2 has been studied in various diseases, including autoimmune diseases, cancer, and infectious diseases. In the context of autoimmune diseases, TNFR2 is thought to contribute to the disease pathology by promoting the survival and function of effector immune cells. In cancer, TNFR2 expression on both tumor cells and immune cells within the tumor microenvironment can promote tumor growth and resistance to therapy. Conversely, the role of TNFR2 in promoting the expansion of Tregs can be beneficial in controlling excessive immune responses during infections.

Given its involvement in various pathological conditions, TNFR2 is considered a potential therapeutic target. Inhibiting TNFR2 signaling has been proposed as a strategy to treat autoimmune diseases and cancer. Conversely, activating TNFR2 signaling could be beneficial in diseases where enhancing immune tolerance or controlling inflammation is desired.

Research Directions

Research on TNFR2 is focused on understanding its complex role in the immune system and its implications in disease. Studies are ongoing to elucidate the signaling pathways activated by TNFR2 and how they interact with other signaling pathways. Additionally, there is interest in developing specific agonists and antagonists of TNFR2 for therapeutic purposes. These agents could provide new treatment options for diseases where TNFR2 signaling plays a key role.