OX40L-OX40 Interactions: A Possible Target for Gastrointestinal Autoimmune Diseases

Gastrointestinal (GI) autoimmune diseases have a high incidence in developed countries, such as Canada and the US. Some common GI autoimmune diseases include ulcerative colitis and Crohn's Disease. These conditions are not only unpleasant for the patient, but also present a heavy burden on the healthcare system. OX40L, a member of the tumor necrosis family, has been identified as a key player in the pathological inflammatory response, which characterizes GI autoimmune diseases. OX40L is expressed in many cell types, including antigen presenting cells (APCs), T-cells, vascular endothelial cells, mast cells, and natural killer cells. The importance of OX40L-OX40 interactions in inflammatory autoimmune diseases is becoming more evident through different animal models, ranging from nematode models to mouse models. This literature review attempts to summarize the current literature regarding the role of OX40L-OX40 interactions in GI autoimmune inflammatory diseases and comment on its potential for treatment. Various databases, including OVID MedLine and PubMed were used to retrieve articles regarding the role of OX40L-OX40 interactions in the pathogenesis of autoimmune diseases. These articles were then reviewed and summarized in a comprehensive manner. OX40L-OX40 interactions have a strong potential for becoming a treatment target; however, there are still many gaps in the present knowledge, which need to be addressed before more definitive treatments can emerge. It is also suggested that upstream events leading to OX40L activation, such as thymic stromal lymphopoietin (TSLP)-activated dendritic cells, be explored as treatment targets as well. OX40L-OX40 interaction is a possible venue for treatment of GI diseases; however, the underlying mechanisms of actions and the downstream effects of OX40L knock down need to be investigated.