Laboratory of Molecular Immunology, Center for Infectious and Inflammatory Diseases, Sanford|Burnham Medical Research Institute, La Jolla, CA 92037, USA.
Immunol Rev. 2011 Nov;244(1):169-87. doi: 10.1111/j.1600-065X.2011.01064.x.
The tumor necrosis factor (TNF) receptor superfamily member herpesvirus entry mediator (HVEM) (TNFRSF14) regulates T-cell immune responses by activating both inflammatory and inhibitory signaling pathways. HVEM acts as both a receptor for the canonical TNF-related ligands, LIGHT [lymphotoxin-like, exhibits inducible expression, and competes with herpes simplex virus glycoprotein D for HVEM, a receptor expressed on T lymphocytes] and lymphotoxin-α, and as a ligand for the immunoglobulin superfamily proteins BTLA (B and T lymphocyte attenuator) and CD160, a feature distinguishing HVEM from other immune regulatory molecules. The ability of HVEM to interact with multiple ligands in distinct configurations creates a functionally diverse set of intrinsic and bidirectional signaling pathways that control both inflammatory and inhibitory responses. The HVEM system is integrated into the larger LTβR and TNFR network through extensive shared ligand and receptor usage. Experimental mouse models and human diseases indicate that dysregulation of HVEM network may contribute to autoimmune pathogenesis, making it an attractive target for drug intervention.
肿瘤坏死因子（TNF）受体超家族成员疱疹病毒进入介体（HVEM）（TNFRSF14）通过激活炎症和抑制信号通路来调节 T 细胞免疫反应。HVEM 既是经典 TNF 相关配体的受体，如 LIGHT[淋巴毒素样，表达可诱导，与单纯疱疹病毒糖蛋白 D 竞争 HVEM，HVEM 是 T 淋巴细胞上表达的受体]和淋巴毒素-α，也是免疫球蛋白超家族蛋白 BTLA（B 和 T 淋巴细胞衰减器）和 CD160 的配体，这一特征将 HVEM 与其他免疫调节分子区分开来。HVEM 与多种配体以不同的构象相互作用的能力产生了一套功能多样的内在和双向信号通路，控制着炎症和抑制反应。HVEM 系统通过广泛的共用配体和受体的使用与更大的 LTβR 和 TNFR 网络整合在一起。实验小鼠模型和人类疾病表明，HVEM 网络的失调可能导致自身免疫发病机制，使其成为药物干预的一个有吸引力的靶点。
