PDF(Pubmed)
Abstract：
Interleukin (IL)-22 is a cytokine that plays a critical role in intestinal epithelial homeostasis. Its downstream functions are mediated through interaction with the heterodimeric IL-22 receptor and subsequent activation of signal transducer and activator of transcription 3 (STAT3). IL-22 signaling can induce transcription of genes necessary for intestinal epithelial cell proliferation, tissue regeneration, tight junction fortification, and antimicrobial production. Recent studies have also implicated IL-22 signaling in the regulation of intestinal epithelial fucosylation in mice. However, whether IL-22 regulates intestinal fucosylation in human intestinal epithelial cells and the molecular mechanisms that govern this process are unknown. Here, in experiments performed in human cell lines and human-derived enteroids, we show that IL-22 signaling regulates expression of the B3GNT7 transcript, which encodes a β1-3-N-acetylglucosaminyltransferase that can participate in the synthesis of poly-N-acetyllactosamine (polyLacNAc) chains. Additionally, we find that IL-22 signaling regulates levels of the α1-3-fucosylated Lewis X (Lex) blood group antigen, and that this glycan epitope is primarily displayed on O-glycosylated intestinal epithelial glycoproteins. Moreover, we show that increased expression of B3GNT7 alone is sufficient to promote increased display of Lex-decorated carbohydrate glycan structures primarily on O-glycosylated intestinal epithelial glycoproteins. Together, these data identify B3GNT7 as an intermediary in IL-22-dependent induction of fucosylation of glycoproteins and uncover a novel role for B3GNT7 in intestinal glycosylation.
摘要：
白细胞介素(IL)-22是在肠上皮稳态中起关键作用的细胞因子。其下游功能通过与异二聚体IL-22受体的相互作用以及随后的信号转导和转录激活因子3（STAT3）的激活来介导。IL-22信号传导可以诱导肠上皮细胞增殖所必需的基因的转录，组织再生，紧密连接设防，和抗菌生产。最近的研究还涉及IL-22信号传导在小鼠肠上皮岩藻糖基化的调节中。然而,IL-22是否调节人肠上皮细胞的肠岩藻糖基化以及控制该过程的分子机制尚不清楚。这里,在人类细胞系和人类来源的类肠样物质中进行的实验中，我们显示IL-22信号调节B3GNT7转录本的表达，它编码β1-3-N-乙酰葡糖胺转移酶，该酶可以参与聚N-乙酰乳糖胺（polyLacNAc）链的合成。此外,我们发现IL-22信号调节α1-3-岩藻糖基化的LewisX（Lex）血型抗原的水平，并且该聚糖表位主要显示在O-糖基化的肠上皮糖蛋白上。此外，我们表明，单独的B3GNT7的表达增加足以促进Lex修饰的碳水化合物聚糖结构主要在O-糖基化的肠上皮糖蛋白上的显示增加。一起,这些数据确定B3GNT7是IL-22依赖性诱导糖蛋白岩藻糖基化的中介，并揭示了B3GNT7在肠道糖基化中的新作用。
