Search

Dectin-1, the receptor for beta-glucans, protects host from fungal infection. However, the role of Dectin-1 in intestinal immunity has not been elucidated completely. We found that Dectin-1-deficient (Clec7a−/−) mice were refractory to both dextran sodium sulfate (DSS)- and CD45RBhiCD4+ T cell-induced colitis associated with an increase of regulatory T (Treg) cells. The proportion of lactobacilli, especially Lactobacillus murinus ( L. murinus ), in commensal microflora was increased in Clec7a−/− mouse colon due to accompanied by a decrease of a group of antimicrobial peptides induced by Dectin-1 signaling. L. murinus colonization increased Treg cells in the colon. Oral administration of laminarin, a Dectin-1 antagonist, suppressed the development of DSS-colitis, associated with the increase of L. murinus and Treg cells. The proportion of closely related Lactobacillus species was decreased in inflammatory bowel disease patients. These observations suggest that Dectin-1 regulates the homeostasis of intestinal immunity by controlling Treg cell differentiation through modification of microbiota. [ABSTRACT FROM AUTHOR]

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]