TNFSF18 Specific Neutra™ Antibody Products

Tumor Necrosis Factor Ligand Superfamily Member 18 (TNFSF18), is a cytokine belonging to the TNF superfamily. Structurally, it comprises a transmembrane domain and a C-terminal extracellular domain. It is expressed in various tissues, including immune cells, epithelial cells, and endothelial cells. TNFSF18 is vital in regulating immune responses, particularly in T cell activation and differentiation. It acts through its receptor, TNFRSF18, also known as GITR or AITR. TNFSF18 is involved in immune tolerance, inflammation, and immune-mediated diseases, making it a potential therapeutic target.

Its Gene ID: 8995, UniProtKB ID: Q9UNG2, and OMIM ID: 603898.

TNFSF18/TNFRSF18 Interaction

The interaction between TNFSF18 and its receptor TNFRSF18 is critical in modulating immune responses. Upon binding, TNFSF18 activates TNFRSF18, initiating signal transduction pathways that impact T cell function. Downstream signal transduction involves the activation of MAPK and NF-κB pathways, resulting in enhanced expression of pro-survival and pro-inflammatory genes. This results in enhanced T cell proliferation, cytokine production (such as IL-2 and IFN-γ), and effector T cell function. Furthermore, the TNFSF18/TNFRSF18 interaction promotes the expansion and functional enhancement of regulatory T cells, contributing to immune homeostasis and tolerance. Overall, the TNFSF18/TNFRSF18 interaction orchestrates a balanced immune response by influencing T cell activation, differentiation, and function, thereby impacting immune regulation, inflammation, and immune-mediated diseases.

TNFSF18 in Diseases

Accumulated evidence suggests TNFSF18 is involved in the pathogenesis of autoimmune disorders, cancer, and inflammatory conditions. In autoimmune diseases like rheumatoid arthritis and multiple sclerosis, dysregulated TNFSF18 signaling contributes to aberrant T cell activation and inflammation. Conversely, in cancer, TNFSF18/TNFRSF18 signaling can have both anti-tumorigenic and pro-tumorigenic effects, depending on the tumor microenvironment. It promotes tumor immunity by enhancing T cell responses against cancer cells but can also facilitate tumor evasion by inducing immunosuppressive mechanisms. Additionally, TNFSF18 is involved in allergic diseases, where it modulates immune responses.

Fig.1 Consequences of signaling via GITR and GITRL(TNFSF18) in different cell types.¹

Antibodies Targeting TNFSF18

Neutralizing antibodies targeting TNFSF18 have shown promise in modulating immune responses. By blocking TNFSF18 signaling, these antibodies may inhibit T cell activation and cytokine production, offering potential therapeutic applications in autoimmune diseases and cancer. Research has demonstrated the efficacy of TNFSF18 neutralizing antibodies in preclinical models of autoimmune conditions like inflammatory bowel disease and in enhancing anti-tumor immune responses in various cancers. For instance, ligation of TNFRSF18 by anti-TNFRSF18 antibodies has been studied to lead to the activation or enhancement of the immune response and has been shown to stimulate effector T cells and attenuate regulatory T cell-mediated suppression. Besides, studies have shown that TNFSF18 neutralizing antibodies can suppress inflammation and promote regulatory T cell function, highlighting their potential for controlling immune dysregulation.

Creative Biolabs offers several types of anti-TNFSF18 antibody products that can be used in six applications.

REFERENCE

1. Placke, Theresa, Hans-Georg Kopp, and Helmut Rainer Salih. "Glucocorticoid-induced TNFR-related (GITR) protein and its ligand in antitumor immunity: functional role and therapeutic modulation." Journal of Immunology Research 2010 (2010). Distributed under Open Access license CC BY 3.0, without modification.