Defective leukocyte GM-CSF receptor (CD116) expression and function in inflammatory bowel disease.
Defective leukocyte GM-CSF receptor (CD116) expression and function in inflammatory bowel disease.
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白细胞GM-CSF受体（CD116）表达和功能缺陷在炎症性肠病中。
DOI：
10.1053/j.gastro.2011.03.060
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发表时间：
2011-07
期刊：
影响因子：
29.4
通讯作者：
Colgan SP
中科院分区：
文献类型：
--
作者：
Goldstein JI;Kominsky DJ;Jacobson N;Bowers B;Regalia K;Austin GL;Yousefi M;Falta MT;Fontenot AP;Gerich ME;Golden-Mason L;Colgan SP
炎症性肠病（IBD）是指两种肠道慢性炎症性疾病：溃疡性结肠炎和克罗恩病。IBD由环境因素（例如细菌抗原）引起，在遗传易感宿主中触发免疫应答失调。虽然IBD的基础还不完全清楚，但最近的一些研究表明IBD的发病机制中存在先天免疫应答缺陷。在这方面，对激活先天免疫的疗法（例如重组GM-CSF）有很大兴趣。本研究检测了52例IBD患者和52例健康对照者外周血白细胞GM-CSF受体（CD 116）mRNA和表面蛋白的表达和功能。我们的研究结果表明，与对照组（p<0.001）和疾病对照组（肠易激综合征，p<0.001;类风湿性关节炎，p<0.025）相比，IBD患者的粒细胞和单核细胞CD 116水平均受到显著抑制，但CD 114或IL-3Rα水平没有受到抑制。与克罗恩病相比，溃疡性结肠炎患者中IBD相关的CD 116抑制更为显著（p<0.05），与疾病活动无关（p>0.05），并且不受当前药物治疗的影响（p>0.05）。受试者工作特征（ROC）曲线分析显示，白细胞CD 116表达是IBD的敏感性（85%）和特异性（92%）生物标志物。此外，与对照组相比，粒细胞CD 116介导的功能（STAT 3的磷酸化）降低了IBD粒细胞中CD 116的表达（p<0.001）。这些研究确定了CD 116的抑制是IBD的一个显著特征，并暗示了对GM-CSF的先天免疫应答中的相关缺陷。
Inflammatory bowel disease (IBD) refers to two chronic inflammatory diseases of the intestine: ulcerative colitis and Crohn’s disease. IBD results from environmental factors (e.g. bacterial antigens) triggering a dysregulated immune response in genetically predisposed hosts. While the basis of IBD is incompletely understood, a number of recent studies have implicated defective innate immune responses in the pathogenesis of IBD. In this regard, there is much interest in therapies that activate innate immunity (e.g. recombinant GM-CSF). In this study, we screened expression and function of circulating leukocyte GM-CSF receptor (CD116) mRNA and surface protein in 52 IBD patients and 52 healthy controls. Our results show that both granulocyte and monocyte CD116 levels, but not CD114 or IL-3Rα, were significantly repressed in IBD compared to control (p<0.001) and disease controls (irritable bowel syndrome, IBS, p<0.001; rheumatoid arthritis, RA, p<0.025). IBD-associated CD116 repression was more prominent in patients with ulcerative colitis compared to Crohn’s disease (p<0.05), was independent of disease activity (p>0.05) and was not influenced by current medications (p>0.05). Receiver operating characteristic (ROC) curve analysis revealed that leukocyte CD116 expression is a sensitive (85%) and specific (92%) biomarker for IBD. Moreover, granulocyte CD116-mediated function (phosphorylation of STAT3) paralleled decreased expression of CD116 in IBD granulocytes compared to control (p<0.001). These studies identify repression of CD116 as a distinguishing feature of IBD and implicate an associated defect in innate immune responses toward GM-CSF.
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影响因子：
29.4
作者：
Han X;Uchida K;Jurickova I;Koch D;Willson T;Samson C;Bonkowski E;Trauernicht A;Kim MO;Tomer G;Dubinsky M;Plevy S;Kugathsan S;Trapnell BC;Denson LA
通讯作者：
Denson LA
影响因子：
9.1
作者：
Marks DJ;Rahman FZ;Sewell GW;Segal AW
通讯作者：
Segal AW
影响因子：
24.5
作者：
Satsangi, J.;Silverberg, M. S.;Colombel, J-F
通讯作者：
Colombel, J-F
影响因子：
24.5
作者：
Valentine, J. F.;Fedorak, R. N.;Humphries, T. J.
通讯作者：
Humphries, T. J.
影响因子：
15.9
作者：
Weissmueller, Thomas;Campbell, Eric L.;Colgan, Sean P.
通讯作者：
Colgan, Sean P.