Salim Sa'ad Y, Silva Manuel A, Keita Asa V, Larsson Marie, Andersson Peter, Magnusson Karl-Eric, Perdue Mary H, Söderholm Johan D
Divisions of Surgery, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
Am J Pathol. 2009 Jan;174(1):82-90. doi: 10.2353/ajpath.2009.080273. Epub 2008 Dec 18.
Recurrent Crohn's disease originates with small erosions in the follicle-associated epithelium overlying the Peyer's patches. Animal studies have illustrated mucosal immune regulation by dendritic cells located in the subepithelial dome. The aim of this study was to characterize the dendritic cells at this specific site in patients with Crohn's disease. Ileal tissues were obtained after surgery performed on Crohn's patients; ileal samples from noninflammatory bowel disease and ulcerative colitis served as standard and inflammatory controls, respectively. Flow cytometry of isolated intestinal mononuclear cells showed a larger subset of dendritic cells in Crohn's samples compared with controls. This finding was corroborated by confocal microscopy, showing enhanced infiltrates of cells positive for the dendritic cell markers, DC-SIGN(+) and CD83(+), in the subepithelial dome. Moreover, the CD83(+) cells in Crohn's tissues showed reduced expression of the lymph node migratory receptor, CCR7, possibly contributing to the high numbers of dendritic cells. After exposure to nonpathogenic Escherichia coli in Ussing chambers, dendritic cells in the subepithelial dome of Crohn's disease demonstrated increased co-localization with translocated bacteria. Immunohistochemical results revealed that DC-SIGN(+) cells in Crohn's tissues were found to express toll-like receptor 4 and produce tumor necrosis factor-alpha. In conclusion, nonmigrating dendritic cells that accumulate in the subepithelial dome and internalize nonpathogenic bacteria may be important for the onset and perpetuation of mucosal inflammation in Crohn's disease.
复发性克罗恩病起源于派尔集合淋巴结上方滤泡相关上皮的小糜烂。动物研究表明，位于上皮下圆顶的树突状细胞可调节黏膜免疫。本研究的目的是对克罗恩病患者这一特定部位的树突状细胞进行特征描述。对克罗恩病患者进行手术后获取回肠组织；分别将来自非炎症性肠病和溃疡性结肠炎的回肠样本作为标准对照和炎症对照。对分离出的肠道单核细胞进行流式细胞术检测发现，与对照组相比，克罗恩病样本中的树突状细胞亚群更大。共聚焦显微镜证实了这一发现，显示上皮下圆顶中树突状细胞标志物DC-SIGN(+)和CD83(+)阳性的细胞浸润增强。此外，克罗恩病组织中的CD83(+)细胞显示淋巴结迁移受体CCR7的表达降低，这可能是导致树突状细胞数量增多的原因之一。在尤斯灌流小室中接触非致病性大肠杆菌后，克罗恩病患者上皮下圆顶中的树突状细胞与易位细菌的共定位增加。免疫组织化学结果显示，克罗恩病组织中的DC-SIGN(+)细胞表达Toll样受体4并产生肿瘤坏死因子-α。总之，在上皮下圆顶中积聚并内化非致病性细菌的非迁移性树突状细胞可能对克罗恩病黏膜炎症的发生和持续存在起重要作用。
