Intestinal heat shock protein 110 regulates expression of CD1d on intestinal epithelial cells
Intestinal heat shock protein 110 regulates expression of CD1d on intestinal epithelial cells
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DOI：
10.1172/jc1200317241
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发表时间：
2003-09-01
影响因子：
15.9
通讯作者：
Blumberg, RS
中科院分区：
文献类型：
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作者：
Colgan, SP;Pitman, RS;Blumberg, RS
CD 1d在专职和非专职APC（包括肠上皮细胞（IEC））的表面表达，在将糖脂抗原呈递给T细胞亚群中发挥作用。在任何细胞类型中调节CD 1d表达的机制都是未知的。为了研究CD 1d表达受肠腔内存在的外源性因素影响的可能性，在正常人肠的内腔内容物（LC）存在下培养后，分析了几种IEC系中的CD 1d表达。暴露的结肠衍生的细胞系T84，HT-29，和Caco-2可溶性LC导致在一个显着的诱导CD 1d的表达，确定通过RT-PCR，共聚焦显微镜，细胞表面ELISA和Western印迹分析。同样，将人IEC暴露于从特定无病原体和无菌条件下饲养的小鼠中分离的LC也导致诱导CD 1d表达，在小肠中观察到最大的CD 1d诱导活性。人CD 1d诱导活性的生物化学和生物物理学表征确定热休克蛋白110（Hsp 110）作为LC的主要功能组分，有助于CD 1d表面调节，免疫定位研究揭示了Hsp 110在体内人IEC亚群中的表达。这些数据支持存在一种新的自分泌途径的CD 1d调节热休克蛋白110。
CD1d is expressed on the surface of professional and nonprofessional APCs, including intestinal epithelial cells (IECs), for a role in the presentation of glycolipid-based antigens to subsets of T cells. The mechanisms that regulate CD1d expression in any cell type are unknown. To investigate the possibility that expression of CD1d is influenced by exogenous factors present within the intestinal lumen, CD1d expression was analyzed in several IEC lines after culturing in the presence of lumenal contents (LC) of the normal human intestine. Exposure of the colon-derived cell lines T84, HT-29, and Caco-2 to soluble LC resulted in a marked induction of CD1d expression as determined by RT-PCR, confocal microscopy, cell surface ELISA, and Western blot analysis. Similarly, exposure of human IECs to LC isolated from mice bred in both specific pathogen-free and germfree conditions also resulted in the induction of CD1d expression, with the maximum CD1d-inducing activity observed in the small intestine. Biochemical and biophysical characterization of the human CD1d-inducing activity identified heat shock protein 110 (Hsp110) as a major functional component of the LC that contributes to CD1d surface regulation, and immunolocalization studies revealed Hsp110 expression in subsets of human IECs in vivo. These data support the presence of a novel autocrine pathway of CD1d regulation by Hsp110.