TNFRSF18, also known as Glucocorticoid-induced TNF receptor related protein (GITR), is a protein found on the surface of certain immune cells. It is a member of the tumor necrosis factor receptor superfamily, a group of proteins involved in regulating various cellular processes. Its presence on immune cells highlights its involvement in the body’s defense mechanisms.
How TNFRSF18 Works in the Body
TNFRSF18 functions as a co-stimulatory molecule, primarily on T cells, which are a type of white blood cell central to immune responses. When TNFRSF18 binds to its specific partner molecule, TNFSF18 (also known as GITRL), it triggers signals inside the T cell. This interaction helps to promote the activation, growth, and survival of effector T cells, which are responsible for directly attacking infected cells or cancer cells.
TNFRSF18 also influences the activity of regulatory T cells (Tregs), a specialized type of T cell that helps to maintain immune tolerance and prevent the immune system from attacking the body’s own tissues. While TNFRSF18 is expressed at low levels on resting T cells, its expression increases on activated T cells and is notably present on regulatory T cells. The signals generated through TNFRSF18 can reduce the suppressive ability of these regulatory T cells, thereby allowing other immune cells to become more active.
TNFRSF18 and Health Conditions
The involvement of TNFRSF18 extends to various health conditions, showcasing its dual influence on the immune system. In the context of cancer, TNFRSF18 signaling can boost anti-tumor immune responses. By activating effector T cells and potentially reducing the suppressive activity of regulatory T cells within the tumor environment, TNFRSF18 can help the immune system recognize and eliminate cancer cells. This makes it a target for developing new cancer immunotherapies aimed at unleashing a stronger immune attack against tumors.
Conversely, dysregulation of TNFRSF18 can contribute to autoimmune diseases. When the immune system becomes overly active or loses its ability to distinguish between self and non-self, it can lead to conditions like rheumatoid arthritis or multiple sclerosis. In some autoimmune diseases, TNFRSF18 is found at higher levels on regulatory T cells, and its activation can sometimes promote inflammation or T cell hyperactivity, contributing to the disease.
Targeting TNFRSF18 in Medicine
Scientists and medical researchers are actively exploring ways to harness TNFRSF18 for therapeutic purposes. One approach involves using agonistic antibodies, which are designed to mimic the natural ligand TNFSF18 and activate TNFRSF18. In cancer treatment, activating TNFRSF18 with such antibodies aims to stimulate effector T cells and potentially overcome the immune suppression often found in tumors, thereby enhancing the body’s ability to fight cancer. These agonistic antibodies are currently undergoing clinical trials to assess their effectiveness in patients.
For autoimmune diseases, the strategy might involve antagonistic approaches to block TNFRSF18 activity. By inhibiting TNFRSF18, researchers aim to dampen excessive immune responses and reduce inflammation that characterizes these conditions. This could involve using antibodies that prevent TNFSF18 from binding to TNFRSF18, or other molecules that interfere with its signaling pathways.