Roles of lymphocyte Kv1.3-channels in gut mucosal immune system: Novel therapeutic implications for inflammatory bowel disease

In the gastrointestinal mucosal immune system, T-lymphocytes are activated to produce pro-inflammatory cytokines, and the over-activation of the lymphocytes is primarily responsible for the development of inflammatory bowel disease (IBD). Despite our understanding of the molecular involvement in the activation of lymphocytes, we know little about the physiological involvement. Circulating T-lymphocytes or those derived from thymus predominantly express delayed rectifier K+-channels (Kv1.3) in their plasma membranes and these channels play crucial roles in inducing the lymphocyte activation and proliferation. In the pathogenesis of chronic renal failure, these channels, which are overexpressed in proliferating lymphocytes within the kidneys, are responsible for the progression of the disease. Since the over-activation of cellular immunity is also involved in the pathogenesis of IBD, T-lymphocytes in the gastrointestinal mucosa could share the same stimulatory mechanisms with those in the inflamed kidneys. Therefore, we hypothesize here that T-lymphocytes in the gastrointestinal mucosa would also be stimulated by the activation of the Kv1.3-channels expressed in their plasma membranes, and that the overexpression of the channels would contribute to the development of IBD. Our hypothesis is unique because it sheds light for the first time on a physiological mechanism by which T-lymphocytes are activated in the gut mucosal immune system. It is also important because our idea could have novel therapeutic implications for IBD, in which the over-activation of the lymphocytes is responsible for the pathogenesis.