TNFSF14

What is TNFSF14 protein?

TNFSF14 gene (TNF superfamily member 14) is a protein coding gene which situated on the short arm of chromosome 19 at locus 19p13. The protein encoded by this gene is a member of the tumor necrosis factor (TNF) ligand family. This protein is a ligand for TNFRSF14, which is a member of the tumor necrosis factor receptor superfamily, and which is also known as a herpesvirus entry mediator (HVEM). This protein may function as a costimulatory factor for the activation of lymphoid cells and as a deterrent to infection by herpesvirus. This protein has been shown to stimulate the proliferation of T cells, and trigger apoptosis of various tumor cells. The TNFSF14 protein is consisted of 240 amino acids and TNFSF14 molecular weight is approximately 26.4 kDa.

What is the function of TNFSF14 protein?

The TNFSF14 protein, also known as LIGHT, is a member of the tumor necrosis factor superfamily and is expressed primarily on activated T cells, natural killer cells (NK cells), and immature dendritic cells. LIGHT can act as a soluble and cell-surface bound type II membrane protein and must interact in its trimer form with its two main functional receptors, the herpesvirus entry mediator (HVEM) and the lymphotoxin-beta receptor (LTβR). LIGHT signaling through these receptors has different functions that depend on cell type, but interactions with both types of receptors have immune-related implications in tumor biology. LIGHT has shown potential in tumor immunotherapy because of its ability to promote anti-tumor immune responses by altering the tumor microenvironment (TME). In addition, LIGHT-LTβR signaling is also responsible for creating highly efficient endothelial veins (HEVs), which are the primary sites where white blood cells leak into the target tissue.

TNFSF14 related signaling pathway

TNFSF14 exhibits inducible expression, and competes with HSV dUTPase for binding to herpesvirus entry mediator, a receptor expressed by T lymphocytes), interacts with its receptors, HVEM and LTβR, to initiate downstream signaling cascades. This interaction can lead to activation of the NF-κB pathway, promoting inflammation and immune cell survival, or induce apoptosis through the extrinsic apoptotic pathway, depending on the cellular context and receptor engagement. The balance between these effects is essential for maintaining immune homeostasis and preventing autoimmunity or chronic inflammation. Dysregulation of this pathway has been implicated in various diseases, including autoimmune disorders and cancer, highlighting its significance in both immune modulation and disease pathogenesis.

TNFSF14 related diseases

TNFSF14-related diseases encompass a spectrum of conditions primarily associated with dysregulated immune responses and inflammation. This includes autoimmune disorders such as rheumatoid arthritis, where overactive TNFSF14 signaling can contribute to joint destruction and chronic inflammation. Additionally, TNFSF14's role in apoptosis regulation links it to cancer development, particularly in malignancies where apoptosis resistance is a hallmark feature. Furthermore, its involvement in T cell co-stimulation suggests a potential role in transplant rejection and graft-versus-host disease. The fine balance between promoting immune activation and apoptosis underscores the complexity of TNFSF14's involvement in health and disease, making it a critical target for therapeutic interventions aimed at modulating immune system activity.

Fig1. Schematic diagram of the potential effect of LIGHT in promoting cardiac fibrosis and atrial fibrillation vulnerability. (Yirong Wu, 2023)

Bioapplications of TNFSF14

By interacting with its receptors, HVEM and LTβR, rhTNFSF14 can either enhance or suppress immune cell activity, depending on the context. This dual capacity makes it a promising therapeutic candidate for conditions characterized by excessive inflammation, such as rheumatoid arthritis and psoriasis, where inhibiting its signaling may alleviate symptoms. Conversely, in scenarios requiring immune enhancement, such as certain cancer immunotherapies, stimulating the TNFSF14 pathway could boost anti-tumor immunity. Additionally, its role in apoptosis regulation suggests potential applications in managing cancers by promoting cell death in malignant cells. Thus, rhTNFSF14 holds significant promise for advancing treatments across a range of immune-mediated diseases, leveraging its ability to fine-tune immune system function.