Increased expression of fractalkine and its receptor CX3CR1 in canine inflammatory bowel disease and their possible role in recruitment of intraepithelial lymphocytes
Increased expression of fractalkine and its receptor CX3CR1 in canine inflammatory bowel disease and their possible role in recruitment of intraepithelial lymphocytes
复制标题
DOI：
10.1016/j.vetimm.2012.04.021
复制
发表时间：
2012-08-15
影响因子：
1.8
通讯作者：
Tsujimoto, Hajime
中科院分区：
文献类型：
--
作者：
Maeda, Shingo;Ohno, Koichi;Tsujimoto, Hajime
Fractalkine/CX(3)CL1与其受体CX(3)CR1的相互作用在多种人类炎症性疾病中发挥重要作用，包括淋巴细胞趋化介导的炎症性肠病(IBD)。本研究旨在探讨Fractalkine和CX(3)CR1在IBD犬淋巴细胞迁移中的作用。34只犬被诊断为IBD，19只健康比格犬作为正常对照。采用实时定量RT-PCR法和酶联免疫吸附试验(ELISA法)分别定量检测肠道中Fractalkine和CX(3)CR1的mRNA和蛋白表达，并用免疫组织化学方法检测Fractalkine在犬肠道的定位。用流式细胞仪检测外周血单个核细胞(PBMCs)和上皮内淋巴细胞(IEL)Cx(3)CR1及表面抗原的表达。IBD犬肠道分裂因子和CX(3)CR1基因表达较健康对照组显著上调。此外，IBD犬的肠粘膜上皮细胞表面的Fractalkine表达较健康犬显著增加。IBD犬Cx(3)、CR1(+)PBMCs显著升高，且与IELs浸润程度呈正相关。这些CX(3)CR1(+)PBMC主要表达细胞毒T细胞标志。几乎所有的IEL细胞都表达CD3，大多数细胞表达CD8而不是CD4，这类似于CX(3)CR1(+)PBMC。这些结果提示，Fractalkine-CX(3)CR1的相互作用可能通过IELs的迁移参与了犬IBD的发病。(C)2012爱思唯尔B.V.保留所有权利。
The interaction between fractalkine/CX(3)CL1 and its receptor CX(3)CR1 has been reported to play an important role in various human inflammatory diseases, including inflammatory bowel disease (IBD) mediated by lymphocyte chemoattraction. The objective of this study was to investigate the role of fractalkine and CX(3)CR1 in lymphocyte migration in canine IBD. IBD was diagnosed in 34 dogs, and 19 healthy beagles were used as normal controls. We quantified intestinal mRNA and protein expression of fractalkine and CX(3)CR1 by real-time RT-PCR and ELISA, respectively, and examined the localization of fractalkine in canine intestine by immunohistochemistry. The expression of CX(3)CR1 and surface antigens on peripheral blood mononuclear cells (PBMCs) and intraepithelial lymphocytes (IELs) was analyzed by flow cytometry. Intestinal fractalkine and CX(3)CR1 mRNA was significantly up-regulated in IBD dogs compared with the healthy control dogs. In addition, fractalkine expression on intestinal epithelial cells was significantly increased in the intestinal mucosa of IBD dogs compared with the healthy dogs. CX(3)CR1(+) PBMCs were significantly elevated in IBD dogs and positively correlated with the histopathological severity of IELs infiltration. These CX(3)CR1(+) PBMCs predominantly expressed markers for cytotoxic T cells. Almost all IELs expressed CD3, and the majority of cells expressed CD8 rather than CD4, which was analogous to the CX(3)CR1(+) PBMCs. These results suggest that the fractalkine-CX(3)CR1 interaction may contribute to the pathogenesis of canine IBD through migration of IELs. (c) 2012 Elsevier B.V. All rights reserved.