255: Inhibition of Dectin-1 signaling suppresses colitis by regulating the balance of intestinal microbiota and cellular immunity.

The intestinal immune system has to take dual tasks; the system should fight against invading pathogens and, at the same time, the system should be tolerant toward commensal microbiota or food components. Dectin-1 is the receptor for beta-glucans expressed in fungal cell walls and activates the immune system to prevent infection. Because beta-glucans are contained in wide variety of foods and commensal microbiota, we investigated the effects of Dectin-1 signaling on the intestinal immunity. We found that Dectin-1-deficient mice were refractory to dextran sodium sulfate-induced colitis, a model for inflammatory bowel diseases, due to expansion of one genus of Gram-positive commensal bacteria in the colon associated with remodification of T cell subpopulations. Furthermore, oral administration of a seaweed-derived Dectin-1 antagonist, inhibited the proinflammatory cytokine production in colonic lamina propria cells and suppressed the development of colitis. These observations suggest that inhibition of Dectin-1 signaling in the colon regulates the balance of intestinal microbiota and cellular immunity, and further suppresses the development of inflammatory bowel diseases. [ABSTRACT FROM AUTHOR]