OX40L signals specifically through the OX40 receptor, which is expressed predominantly on CD4+T cells but also on certain activated CD8+T cells. OX40/OX40L functions as a costimulatory signal, which is required for a productive interaction between antigen presenting cells and their target T-cells. It enhances cell proliferation and survival, and increases expression of regulated on activation, normal T cell expressed and secreted (RANTES) or chemokine ligand 5 (CCL5), interleukins-2 and -3, and interferon-γ (IFNγ). OX40/OX40L signaling plays an important role in immuno-regulatory communication and immune-tolerance. Polymorphisms in the TNFSF4 gene have been associated with autoimmune thyroid diseases (AITDs), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and systemic sclerosis (SSc).
