O040 A novel role of Dectin-1 signaling in promoting intestinal inflammation

Abstract

Introduction Dectin-1, which was first reported as a dentritic cell-specific type II C-type lectin family member, is the receptor for β-1,3 or −1,6-linked glucans (β-glucans), an important cell wall components of fungi and yeasts. Dysregulated response of mucosal immune system toward intraluminal bacteria results in the human inflammatory bowel disease (IBD). Beta-glucan is thought to promote the mucosal immunity in intestines, but the roles of Dectin-1 in mucosal immune system are still unknown. Methods To investigate the potential role of Dectin-1 in development of IBD, we administrated Decint-1 deficient ( clec7a −/− ) mice with dextran sulfate sodium (DSS) to induce the acute ulcerative colitis and found that clec7a −/− mice were significantly resistant to DSS-induced colitis compared to wild-type (WT) mice, associated with lower production of TNF-α and reduced numbers of neutrophils and macrophages in lamina propria of colon. Results Pre-treatment of dectin-1 antagonist ligand Laminarin could suppress the acute intestinal inflammation induced by DSS. Metagenome analysis using bacterial 16s rRNA genes revealed significantly change of the microflora in small intestine and colon of clec7a −/− mice compared to WT mice, and administration of intestinal bacteria of clec7a −/− mice in SPF condition to germ-free WT mice also showed resistant to DSS-induced colitis. Conclusion These new findings identify Dectin-1 as novel factor in promotion of acute colitis by directly inducing proinflammatory cytokines and by regulating the balance of intestinal microbiota. Blockade of Dectin-1 signaling suggests new therapeutic strategies for inflammatory bowel diseases.