Cell death in the colonic epithelium during inflammatory bowel diseases: CD95/Fas and beyond

CD95 is a member of the death receptor family. It is a prototypical inducer of apoptosis that, upon binding of its cognate ligand (CD95L), forms a death-inducing signaling complex composed of adaptor molecules and initiator caspases that transmit the apoptosis signal. The CD95/CD95L system was implicated in the etiology of inflammatory bowel disease (IBD) based, primarily, on the finding that CD95 is highly expressed in the intestinal epithelial cells and that epithelial apoptosis is increased in IBD. In recent years it has been recognized that CD95, while playing an important role as an apoptosis-inducing receptor in the immune system, also has multiple nonapoptotic functions on nonimmune cells. This review critically discusses the data on the possible function of CD95 as an apoptosis-inducing receptor in IBD and discusses alternative mechanisms for epithelial cell loss in IBD.