Article

Genetic Association Analysis of the Functional c.714T>G Polymorphism and Mucosal Expression of Dectin-1 in Inflammatory Bowel Disease

Department of Gastroenterology and Hepatology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
PLoS ONE (Impact Factor: 3.23). 11/2009; 4(11):e7818. DOI: 10.1371/journal.pone.0007818
Source: PubMed

ABSTRACT

Dectin-1 is a pattern recognition receptor (PRR) expressed by myeloid cells that specifically recognizes β-1,3 glucan, a polysaccharide and major component of the fungal cell wall. Upon activation, dectin-1 signaling converges, similar to NOD2, on the adaptor molecule CARD9 which is associated with inflammatory bowel disease (IBD). An early stop codon polymorphism (c.714T>G) in DECTIN-1 results in a loss-of-function (p.Y238X) and impaired cytokine responses, including TNF-α, interleukin (IL)-1β and IL-17 upon in vitro stimulation with Candida albicans or β-glucan. The aim of the present study was to test the hypothesis that the DECTIN-1 c.714T>G (p.Y238X) polymorphism is associated with lower disease susceptibility or severity in IBD and to investigate the level of dectin-1 expression in inflamed and non-inflamed colon tissue of IBD patients.

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    • "However, little is known about the role of dectin-1 in maintaining intestinal homeostasis. Dectin-1 is highly expressed in the intestine [25] and humans with CD have also been shown to have increased numbers of dectin-1 expressing inflammatory cells in the intestine compared with healthy individuals [26]. Together this implies that dectin-1 may play a role in intestinal immunity. "
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    • "CARD9 is a caspase recruitment-domain–containing signaling protein expressed in various tissues.10,11 It is closely associated with several inflammatory diseases, including tuberculosis, inflammatory bowel disease, tuberculosis, and ankylosing spondylitis.13,29,30 In CARD9−/− mice, stimulation of dendritic cells caused a marked decrease in the production of IL-2, -6, and -10, and TNF-α and decreased numbers of Th17 cells.31,32,33 "
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