Bacterial Sensor Triggering Receptor Expressed on Myeloid Cells-2 Regulates the Mucosal Inflammatory Response
Bacterial Sensor Triggering Receptor Expressed on Myeloid Cells-2 Regulates the Mucosal Inflammatory Response
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DOI：
10.1053/j.gastro.2012.10.040
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发表时间：
2013-02-01
期刊：
影响因子：
29.4
通讯作者：
Danese, Silvio
中科院分区：
文献类型：
--
作者：
Correale, Carmen;Genua, Marco;Danese, Silvio
背景和目标：髓样细胞上表达的触发受体（TREM）-2是在巨噬细胞、树突状细胞和小胶质细胞上检测到的表面受体，其结合酵母和革兰氏阳性和革兰氏阴性细菌上的重复阴离子基序。关于TREM-2在肠道中的表达和功能或其在炎症性肠病（IBD）中的作用知之甚少。我们研究了TREM-2在肠固有层中的表达及其在结肠炎症发展中的作用。方法：我们测量了从IBD或癌症患者（对照）收集的手术标本的固有层单核细胞中TREM-2的水平。我们分析了TREM-2敲除小鼠和野生型小鼠中结肠炎的发展。从小鼠中分离结肠样品，并分析细胞因子表达、细菌吞噬作用、结肠隐窝增殖、固有层单核细胞功能和卵清蛋白对T细胞的活化。研究结果：TREM-2在对照患者的结肠样本中几乎不存在，但在IBD患者的炎症粘膜中水平显著较高;它主要由CD11c（+）细胞表达。TREM-2的水平随着小鼠中急性或慢性结肠炎的诱导而增加。与野生型小鼠相比，TREM-2敲除小鼠发生的结肠炎不太严重;敲除小鼠体重减轻较少，疾病活动指数较低，并且在内窥镜分析中具有较小的粘膜病变。来自TREM-2敲除小鼠的结肠树突状细胞产生较低水平的炎性细胞因子，并且与来自野生型小鼠的细胞相比具有降低的细菌杀伤和T细胞活化水平。结论：TREM-2在小鼠结肠炎的发展过程中促进粘膜炎症。TREM-2的水平在IBD患者的发炎粘膜内增加，表明其作为治疗靶点的潜力。
BACKGROUND AND AIMS: Triggering receptor expressed on myeloid cells (TREM)-2 is a surface receptor detected on macrophages, dendritic cells, and microglia that binds repeated anionic motifs on yeast and Gram-positive and Gram-negative bacteria. Little is known about TREM-2 expression and function in the intestine or its role in inflammatory bowel disease (IBD). We investigated the expression of TREM-2 in the intestinal lamina propria and its role in the development of colonic inflammation. METHODS: We measured levels of TREM-2 in lamina propria mononuclear cells from surgical specimens collected from patients with IBD or cancer (controls). We analyzed the development of colitis in TREM-2 knockout and wild-type mice. Colon samples were isolated from mice and analyzed for cytokine expression, phagocytosis of bacteria, proliferation in colonic crypts, lamina propria mononuclear cell function, and T-cell activation by ovalbumin. RESULTS: TREM-2 was virtually absent from colon samples of control patients, but levels were significantly higher in within the inflamed mucosa of patients with IBD; it was mainly expressed by CD11c(+) cells. Levels of TREM-2 increased as acute or chronic colitis was induced in mice. TREM-2 knockout mice developed less severe colitis than wild-type mice; the knockout mice lost less body weight, had a lower disease activity index, and had smaller mucosal lesions in endoscopic analysis. Colon dendritic cells from TREM-2 knockout mice produced lower levels of inflammatory cytokines and had reduced levels of bacterial killing and T-cell activation than cells from wild-type mice. CONCLUSIONS: TREM-2 contributes to mucosal inflammation during development of colitis in mice. Levels of TREM-2 are increased within the inflamed mucosa of patients with IBD, indicating its potential as a therapeutic target.