CCL25/CCR9 promotes the induction and function of CD103 on intestinal intraepithelial lymphocytes
CCL25/CCR9 promotes the induction and function of CD103 on intestinal intraepithelial lymphocytes
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DOI：
10.1002/eji.200425125
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发表时间：
2004-10-01
影响因子：
5.4
通讯作者：
Agace, WW
中科院分区：
文献类型：
--
作者：
Ericsson, A;Svensson, M;Agace, WW
整合素CD103和趋化因子受体CCR9在小肠CD8(+)上皮内淋巴细胞(IEL)、小鼠CD8(+)T细胞和少量效应/记忆性CD8(+)T细胞上共表达，提示CCR9在调节CD103的表达和功能方面具有潜在的作用。在此，我们证明CD103与CCR9不同，CD8(+)T细胞在肠系膜淋巴结被激活后表达下调，最初进入小肠上皮的效应CD8(+)T细胞是CCR9(+)CD103(-)。CD103在野生型CD8(+)T细胞进入小肠上皮后迅速被诱导，而CCR9(-/-)CD8(+)T细胞在这一部位对CD103的诱导表现出明显的延迟。此外，CCR9配体CCL25可诱导CD8(+)小肠IEL与小鼠E-cadherin人Fc(MEFc)融合蛋白的一过性、剂量依赖和百日咳毒素敏感的CD103介导的黏附。综上所述，这些结果表明CCR9/CCL25在促进CD103对CD8(+)IEL的诱导和功能中起作用，并提示这种趋化因子受体/趋化因子对可能调节小肠粘膜中淋巴细胞-上皮细胞的相互作用。
The integrin CD103 and the chemokine receptor CCR9 are co-expressed on small intestinal CD8(+) intraepithelial lymphocytes (IEL), naive murine CD8(+) T cells and by a small population of effector/memory CD8(+) T cells, indicating a potential role for CCR9 in regulating CD103 expression and function. Here, we demonstrate that CD103, in contrast to CCR9, is downregulated on CD8(+) T cells following their activation in mesenteric lymph nodes and that effector CD8(+) T cells upon initial entry into the small intestinal epithelium are CCR9(+)CD103(-). CD103 was rapidly induced on wild-type CD8(+) T cells subsequent to their entry into the small intestinal epithelium, however, CCR9(-/-) CD8(+) T cells exhibited a significant delay in CD103 induction at this site. In addition, the CCR9 ligand, CCL25, that is constitutively expressed in the small intestinal epithelium, induced transient, dose-dependent and pertussis toxin-sensitive CD103-mediated adhesion of CD8(+) small intestinal IEL to a murine E-cadherin human Fc (mEFc) fusion protein. Together, these results demonstrate a role for CCR9/CCL25 in promoting the induction and function of CD103 on CD8(+) IEL and suggest that this chemokine receptor/chemokine pair may function to regulate lymphocyte-epithelial interactions in the small intestinal mucosa.