Regulated MIP-3α/CCL20 production by human intestinal epithelium:: mechanism for modulating mucosal immunity
Regulated MIP-3α/CCL20 production by human intestinal epithelium:: mechanism for modulating mucosal immunity
复制标题
DOI：
10.1152/ajpgi.2001.280.4.g710
复制
发表时间：
2001-04-01
影响因子：
4.5
通讯作者：
Kagnoff, MF
中科院分区：
文献类型：
--
作者：
Izadpanah, A;Dwinell, MB;Kagnoff, MF
人肠上皮细胞分泌一系列趋化因子，已知其发出在先天粘膜免疫中重要的中性粒细胞和单核细胞的运输信号。我们推测，肠上皮细胞也可能有能力发挥作用，在信号宿主的适应性免疫。CC趋化因子巨噬细胞炎性蛋白（MIP）-3 α/CCL 20对未成熟树突状细胞和CD 45 RO（+）T细胞具有趋化性，这些细胞是宿主适应性免疫系统的重要组成部分。在这些研究中，我们证明了MIP-3 α的广泛生产和调节表达的人肠上皮细胞。几种肠上皮细胞系显示组成型表达MIP-3 α mRNA。此外，MIP-3 α mRNA的表达和蛋白质的生产上调刺激的肠上皮细胞与促炎细胞因子肿瘤坏死因子-α或白细胞介素-1 α或响应感染的肠道细菌病原体沙门氏菌或肠侵袭性大肠杆菌。此外，MIP-3 α显示出作为核因子-κ B靶基因的功能。体外结果在体内通过增加的MIP-3 α表达而得到证实，MIP-3 α表达在经精氨酸刺激或细菌感染的人肠异种移植物的上皮中以及在发炎的人结肠的上皮中。粘液T细胞、其他粘膜单核细胞和肠上皮细胞表达MIP-3 α的同源受体CCR 6。人肠上皮细胞MIP-3 α的组成性和调节性表达与上皮细胞产生的MIP-3 α在调节粘膜适应性免疫应答中的作用一致。
Human intestinal epithelial cells secrete an array of chemokines known to signal the trafficking of neutrophils and monocytes important in innate mucosal immunity. We hypothesized that intestinal epithelium may also have the capacity to play a role in signaling host adaptive immunity. The CC chemokine macrophage inflammatory protein (MIP)-3 alpha /CCL20 is chemotactic for immature dendritic cells and CD45RO(+) T cells that are important components of the host adaptive immune system. In these studies, we demonstrate the widespread production and regulated expression of MIP-3 alpha by human intestinal epithelium. Several intestinal epithelial cell lines were shown to constitutively express MIP-3 alpha mRNA. Moreover, MIP-3 alpha mRNA expression and protein production were upregulated by stimulation of intestinal epithelial cells with the proinflammatory cytokines tumor necrosis factor-alpha or interleukin-1 alpha or in response to infection with the enteric bacterial pathogens Salmonella or enteroinvasive Escherichia coli. In addition, MIP-3 alpha was shown to function as a nuclear factor-kappaB target gene. In vitro findings were paralleled in vivo by increased expression of MIP-3 alpha in the epithelium of cytokine-stimulated or bacteria-infected human intestinal xenografts and in the epithelium of inflamed human colon. Mucosal T cells, other mucosal mononuclear cells, and intestinal epithelial cells expressed CCR6, the cognate receptor for MIP-3 alpha. The constitutive and regulated expression of MIP-3 alpha by human intestinal epithelium is consistent with a role for epithelial cell-produced MIP-3 alpha in modulating mucosal adaptive immune responses.