OX40/OX40L Signaling Pathway

1. OX40/OX40L Signaling Pathway Tumor necrosis factor receptor superfamily, member 4 (TNFRSF4), also known as CD134 and OX40 receptor, is a fellow of the TNFR-superfamily of receptors. It is a protein which in humans is encoded by the TNFRSF4 gene which contains 9 exons. It also has been demonstrated to have a key role in the survival and homeostasis of effector and memory T cells in transplantation and autoimmunity. OX40 is not constitutively expressed on resting naive T cells, unlike CD28. As a secondary co-stimulatory immune checkpoint molecule, it expresses after 24 to 72 hours following activation; its ligand, OX40L, is also not expressed on resting antigen presenting cells and resting naive T cells, but is following their activation. Expression of OX40 is dependent on full activation of the T cell and the expression of CD28; without CD28, expression of OX40 is delayed and of fourfold lower levels. The function of pathway According to previous introduction, OX40 is not expressed on resting T cells, but is upregulated reasonably late after T cell activation. OX40 is ligated by OX40L when activated T cells bind to APCs. OX40 has no effect on the proliferative abilities of CD4+ cells for the first three days, however after this time proliferation begins to slow and cells die at a greater rate, due to an inability to maintain a high level of PKB(also known as Akt) activity and expression of Bcl-2, Bcl-XL and survivin (survivin protein functions to inhibit caspase activation, thereby leading to negative regulation of apoptosis or programmed cell death). OX40L binds to OX40 receptors on T-cells, preventing them from dying and subsequently increasing cytokine production. OX40 has a key role in the maintenance of an immune response beyond the first few days and onwards to a memory response due to its ability to enhance survival. Besides, OX40 also plays a crucial role in both Th1 and Th2-mediated reactions in vivo. https://www.creative-diagnostics.com/ox40-ox40l-signaling-pathway.htm