Maeda Shingo, Ohno Koichi, Nakamura Kenji, Uchida Kazuyuki, Nakashima Ko, Fukushima Kenjiro, Nakajima Mayumi, Goto-Koshino Yuko, Fujino Yasuhito, Tsujimoto Hajime
Department of Veterinary Internal Medicine, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.
Vet Immunol Immunopathol. 2012 Aug 15;148(3-4):226-35. doi: 10.1016/j.vetimm.2012.04.021. Epub 2012 May 9.
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.
据报道，趋化因子/CX(3)CL1与其受体CX(3)CR1之间的相互作用在多种人类炎症性疾病中发挥重要作用，包括由淋巴细胞趋化介导的炎症性肠病（IBD）。本研究的目的是探讨趋化因子和CX(3)CR1在犬IBD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。我们分别通过实时RT-PCR和ELISA定量检测肠道中趋化因子和CX(3)CR1的mRNA和蛋白表达，并通过免疫组织化学检查趋化因子在犬肠道中的定位。通过流式细胞术分析外周血单核细胞（PBMC）和上皮内淋巴细胞（IEL）上CX(3)CR1和表面抗原的表达。与健康对照犬相比，IBD犬肠道趋化因子和CX(3)CR1 mRNA显著上调。此外，与健康犬相比，IBD犬肠黏膜中肠上皮细胞上的趋化因子表达显著增加。IBD犬中CX(3)CR1(+) PBMC显著升高，且与IEL浸润的组织病理学严重程度呈正相关。这些CX(3)CR1(+) PBMC主要表达细胞毒性T细胞标志物。几乎所有IEL均表达CD3，且大多数细胞表达CD8而非CD4，这与CX(3)CR1(+) PBMC类似。这些结果表明，趋化因子-CX(3)CR1相互作用可能通过IEL迁移促进犬IBD的发病机制。
