Abstract
BackgroundDectin-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.MethodologyParaffin embedded tissue samples from non-inflamed and inflamed colon of IBD patients and from diverticulitis patients were immunohistochemically stained for dectin-1 and related to CD68 macrophage staining. Genomic DNA of IBD patients (778 patients with Crohn's disease and 759 patients with ulcerative colitis) and healthy controls (n = 772) was genotyped for the c.714T>G polymorphism and genotype-phenotype interactions were investigated.Principal FindingsIncreased expression of dectin-1 was observed in actively inflamed colon tissue, as compared to non-inflamed tissue of the same patients. Also an increase in dectin-1 expression was apparent in diverticulitis tissue. No statistically significant difference in DECTIN-1 c.714T>G allele frequencies was observed between IBD patients and healthy controls. Furthermore, no differences in clinical characteristics could be observed related to DECTIN-1 genotype, neither alone, nor stratified for NOD2 genotype.ConclusionsOur data demonstrate that dectin-1 expression is elevated on macrophages, neutrophils, and other immune cells involved in the inflammatory reaction in IBD. The DECTIN-1 c.714T>G polymorphism however, is not a major susceptibility factor for developing IBD.
Highlights
Inflammatory bowel disease (IBD), is an idiopathic, chronic, relapsing inflammatory disorder of the gastrointestinal tract
Our data demonstrate that dectin-1 expression is elevated on macrophages, neutrophils, and other immune cells involved in the inflammatory reaction in inflammatory bowel disease (IBD)
The established association of NOD2 (CARD15) with Crohn’s disease (CD) emphasizes the important role of the intestinal microbiota in the pathogenesis of CD, since NOD2 acts as an intracellular pattern recognition receptor (PRR) recognizing bacterial peptidoglycans[5,6]
Summary
Inflammatory bowel disease (IBD), is an idiopathic, chronic, relapsing inflammatory disorder of the gastrointestinal tract. The established association of NOD2 (CARD15) with CD emphasizes the important role of the intestinal microbiota in the pathogenesis of CD, since NOD2 acts as an intracellular pattern recognition receptor (PRR) recognizing bacterial peptidoglycans[5,6]. Dectin-1 is a pattern recognition receptor (PRR) expressed by myeloid cells that recognizes b-1,3 glucan, a polysaccharide and major component of the fungal cell wall. Dectin-1 signaling converges, similar to NOD2, on the adaptor molecule CARD9 which is associated with inflammatory bowel disease (IBD). 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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