Lymphotoxin beta receptor and Herpesvirus entry mediator (LTBR/HVEM)

LIGHT (TNFSF14) is a cytokine that signals through two primary functional receptors: the Herpesvirus Entry Mediator (HVEM, TNFRSF14) and the Lymphotoxin Beta Receptor (LTBR, TNFRSF3). HVEM is predominantly expressed on immune cells, such as T cells and natural killer (NK) cells, where it acts as a co-stimulatory molecule to enhance T cell activation and survival. In contrast, LTBR is expressed on stromal cells, epithelial cells, and myeloid cells, playing a critical role in lymphoid organogenesis, the production of homeostatic chemokines, and the regulation of tissue-specific inflammation. This receptor system is a key mediator of the communication between immune and stromal cells, influencing both innate and adaptive immunity. Dysregulation of the LIGHT-receptor axis is implicated in various inflammatory diseases, such as inflammatory bowel disease and asthma, as well as in the tumor microenvironment where it can influence T cell infiltration and the formation of tertiary lymphoid structures. Therapeutic strategies include neutralizing antibodies to treat inflammatory conditions or using receptor agonists to stimulate anti-tumor immunity.

Other names

LIGHT receptorsTNFSF14 receptorsLTBRHVEMTNFRSF3TNFRSF14CD270

Neutralization of the LIGHT ligand to prevent binding to HVEM and LTBR (anti-inflammatory); Agonism of LTBR and HVEM to stimulate immune cell recruitment and stromal remodeling (anti-tumor).