|開催日時：||2016年9月23日 11：00 ～ 12：00|
|所属：||La Jolla Institute・教授|
|演題：||Food for Thought:
Mucosal Immune Protection and Regulation Controlled by the Diet.
Environmental factors, such as the microbiome, have critical control over health and disease. Dietary antigens also have a significant influence and a recent study showed that dietary antigens uniquely limit mucosal immunity by inducing Foxp3Treg in the lamina propria of the small intestine. In sharp contrast however in Celiac Disease, gluten-reactive CD4 T cells respond as pathogenic inflammatory effector cells and cause severe destruction of the small intestine barrier. This clearly demonstrates that immune regulation and suppression is of utmost importance to prevent aberrant immune responses against food antigens. The small intestine epithelium, though, is not only exposed to food but it is also the largest and most vulnerable entry port for pathogens. Furthermore, uncontrolled infections of the epithelial cells by intracellular pathogens can lead, not only to pathogen-induced damage but also to excessive recruitment of systemic inflammatory immune cells, which can fuel severe immune pathology. Therefore, although suppression is important, immune regulation at the mucosal epithelium must coincide with rapid and effective protective immunity to quickly eliminate infected intestinal epithelial cells before the pathogen or inflammatory immune cells can cause destruction of the barrier. We recently made a major discovery that might clarify this immunological conundrum. We found that instead of becoming Foxp3Treg, CD4 T helper cells in the small intestine epithelium that respond to dietary antigens convert to protective cytotoxic cells. Moreover, by converting dietary antigen-responding CD4 T cells they also divert away from becoming inflammatory Th1 or Th17 effector cells. Based on these exciting new findings, we postulate that the reprogramming process is an alternative way of immune regulation to prevent aberrant immune responses to the diet. Furthermore, because these cytotoxic CD4 T cells react with immediate protective function in response to antigen re-stimulation in the context of danger signals, we also propose that these diet antigen-responsive protective cells participate in the direct defense against invading pathogens and in doing so prevent excessive pathogen- and/or immune-induced pathology at this fragile mucosal border.