TNFRSF14
Description
The TNFRSF14 (TNF receptor superfamily member 14) is a protein-coding gene located on chromosome 1.
TNFRSF14, also known as HVEM (herpesvirus entry mediator), is a human cell surface receptor belonging to the TNF-receptor superfamily. It is encoded by the TNFRSF14 gene. TNFRSF14 is also known as CD270 and ATAR (another TRAF-associated receptor). TNFRSF14 plays a role in the immune response by binding to various ligands, including TNFSF14/LIGHT, LTA/lymphotoxin-alpha, BTLA, and CD160. These interactions mediate diverse signaling pathways, regulating immune cell survival, differentiation, and effector functions. TNFRSF14 is also involved in the entry of herpes simplex viruses 1 and 2 into cells, acting as a receptor for their envelope glycoprotein D (gD). Mutations in the TNFRSF14 gene have been associated with cases of diffuse large B-cell lymphoma and pediatric-type follicular lymphoma.
TNFRSF14, also known as HVEM, is a receptor for four distinct ligands: TNFSF14/LIGHT, LTA/lymphotoxin-alpha, BTLA, and CD160. This complex interaction network plays a role in both stimulating and inhibiting immune responses. TNFRSF14 signaling is mediated through the TRAF2-TRAF3 E3 ligase pathway, promoting immune cell survival and differentiation. TNFRSF14 is involved in bidirectional cell-cell signaling between antigen presenting cells and lymphocytes. Upon TNFSF14/LIGHT ligation, TNFRSF14 delivers costimulatory signals to T cells, promoting cell proliferation and effector functions. TNFRSF14 interacts with CD160 on NK cells, enhancing IFNG production and anti-tumor immune response. In the context of bacterial infection, TNFRSF14 acts as a signaling receptor on epithelial cells for CD160 from intraepithelial lymphocytes, triggering antimicrobial protein and pro-inflammatory cytokine production. Binding to CD160 on activated CD4+ T cells down-regulates CD28 costimulatory signaling, restricting memory and alloantigen-specific immune response. TNFRSF14 may interact with BTLA in cis (on the same cell) or in trans (on other cells). Cis interactions seem to play an immune regulatory role, inhibiting trans interactions in naive T cells to maintain a resting state. Trans interactions predominate during adaptive immune response, providing survival signals to effector T cells.
TNFRSF14 is also known as ATAR, CD270, HVEA, HVEM, LIGHTR, TR2.
