OX40 Ligand

OX40 ligand (OX40L, TNFSF4, CD252, also gp34 and TAX activation gene 1 product) is the type II transmembrane TNF family ligand for the co-stimulatory receptor OX40. OX40L assembles as a homotrimer, presented on activated antigen-presenting cells-bone marrow dendritic cells, macrophages, Langerhans cells and B cells-after CD40, TLR, RANK or TNF stimulation, and is also expressed on activated endothelial cells, mast cells and natural killer cells. Cell surface OX40L can be cleaved to soluble forms that retain receptor binding. Engagement of OX40 on CD4+ T cells promotes clonal expansion, effector cytokine secretion, survival and memory development while suppressing Treg-mediated inhibition and Th2-to-Th1 plasticity modulation; OX40L-OX40 signals are required for productive follicular helper T-cell-dependent germinal center responses. The OX40L gene lies in systemic lupus erythematosus linkage intervals, and its overexpression drives lupus-like autoimmunity and atherosclerosis in mouse models; tumor-targeted OX40L delivery is being exploited for cancer immunotherapy.