CD40 and multiple sclerosis: In contrast, CD40 is upregulated in various inflammatory disorders and, through ligand engagement, CD40 triggers pro-inflammatory responses in endothelial cells, vascular smooth muscle cells and epithelial cells that play a key role in the pathogenesis of various disorders such as inflammatory bowel disease, systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, graft rejection, and atherosclerosis (22, 23).