Department of Gastroenterology and Hepatology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
PLoS One. 2009 Nov 12;4(11):e7818. doi: 10.1371/journal.pone.0007818.
Dectin-1 is a pattern recognition receptor (PRR) expressed by myeloid cells that specifically recognizes beta-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-alpha, interleukin (IL)-1beta and IL-17 upon in vitro stimulation with Candida albicans or beta-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.
Paraffin 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.
Increased 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.
Our 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.
Dectin-1 是一种模式识别受体 (PRR)，表达于髓系细胞，其特异性识别β-1,3 葡聚糖，这是真菌细胞壁的主要成分之一。在被激活后，dectin-1 的信号传导与 NOD2 类似，集中在衔接分子 CARD9 上，而 CARD9 与炎症性肠病 (IBD) 有关。Dectin-1 中的一个提前终止密码子多态性（c.714T>G）导致功能丧失（p.Y238X）和细胞因子反应受损，包括白念珠菌或β-葡聚糖体外刺激后 TNF-α、白细胞介素 (IL)-1β 和 IL-17。本研究的目的是检验这样一个假设，即 DECTIN-1 c.714T>G (p.Y238X) 多态性与 IBD 的较低疾病易感性或严重程度相关，并研究 IBD 患者的炎症和非炎症结肠组织中 dectin-1 的表达水平。
对 IBD 患者的非炎症和炎症结肠以及憩室炎患者的石蜡包埋组织样本进行 dectin-1 的免疫组织化学染色，并与 CD68 巨噬细胞染色相关。对 IBD 患者（778 例克罗恩病患者和 759 例溃疡性结肠炎患者）和健康对照者（n=772）的基因组 DNA 进行 c.714T>G 多态性的基因分型，并对基因型-表型相互作用进行了研究。
与同一患者的非炎症组织相比，在活动性炎症性结肠组织中观察到 dectin-1 的表达增加。在憩室炎组织中也明显增加了 dectin-1 的表达。在 IBD 患者和健康对照者之间，DECTIN-1 c.714T>G 等位基因频率没有统计学上的显著差异。此外，无论是单独观察，还是分层观察 NOD2 基因型，都没有观察到 DECTIN-1 基因型与临床特征的差异。
我们的数据表明，在 IBD 的炎症反应中，巨噬细胞、中性粒细胞和其他免疫细胞上的 dectin-1 表达增加。然而，DECTIN-1 c.714T>G 多态性并不是 IBD 发病的主要易感因素。
