Tnfrsf14, also known as herpesvirus entry mediator (HVEM), is a member of the tumor necrosis factor (TNF) receptor superfamily. It plays a crucial role in regulating T-cell immune responses by activating both inflammatory and inhibitory signaling pathways. It acts as a receptor for ligands like LIGHT and lymphotoxin-α, and as a ligand for proteins BTLA and CD160, thus creating diverse signaling pathways. It is also integrated into the LTβR and TNFR network [3].

In ovariectomy-induced adipose tissue inflammation, TNFRSF14 deficiency in knockout mice attenuated fat mass increase, infiltration of highly inflammatory CD11c cells in adipose tissue, and glucose metabolism disturbance. TNFRSF14 enhanced CD11c expression via reactive oxygen species generation upon LIGHT engagement, suggesting its role as a redox modulator [2].

In the context of spontaneous abortion, activation of the MITF-TNFRSF14/HVEM signaling in decidual stromal cells (DSCs) promotes autophagy, which in turn facilitates the adhesion and retention of decidual NK cells. Deficiency in this process may lead to spontaneous abortion, and rapamycin can prevent it by activating this axis [1].

In conclusion, Tnfrsf14 is essential in immune regulation and related biological processes. Its role in diseases such as post-menopausal syndrome-related adipose tissue inflammation and spontaneous abortion has been revealed through gene knockout mouse models. Understanding Tnfrsf14 provides insights into these disease mechanisms and potential therapeutic targets.