锌具有抗炎性能，其机制尚不清楚。Zip14（Slc39a14）是受促炎性刺激诱导的锌转运蛋白，在肠上皮细胞（IEC）的基底侧膜中高度表达。开发了小鼠肠上皮特异性Zip14敲除（Zip14ΔIEC）来研究该转运蛋白在肠道上皮细胞中的功能。基因敲除导致肠道通透性增加，IL-6和IFNγ表达增加，轻度内毒素血症和肠道微生物失调。使用RNA测序进行转录组分析，结果显示特定肠道促炎性和紧密连接（TJ）基因的差异表达。转录因子NF-κβ、STAT3和CDX2的结合适当的基因启动子位点支持染色质免疫沉淀分析展示的差异表达。Zip14敲除后，总组蛋白去乙酰化酶（HDAC）和特别是HDAC3活性显著降低。从ΔIEC小鼠获得的肠道器官样品与对照小鼠相比显示TJ和细胞因子基因失调。通过对器官样品进行锌补充，特定基因的差异表达被逆转。我们得出结论：锌依赖的HDAC酶通过Zip14介导的运输获取锌离子，肠道完整性部分通过表观遗传修饰进行控制。 本研究发现，肠上皮特异性锌转运蛋白Zip14（Slc39a14）敲除导致选择性肠道微生物失调和紧密连接蛋白claudin 1和2以及特定与肠道炎症相关的细胞因子差异表达。Zip14敲除降低HDAC活性和锌摄取。使用肠道器官样品，通过锌补充解决claudin 1和2表达缺陷。这些新颖的结果表明，作为必需微量元素的锌通过表观遗传机制影响基因表达。

Zinc has anti-inflammatory properties using mechanisms that are unclear. Zip14 (Slc39a14) is a zinc transporter induced by proinflammatory stimuli and is highly expressed at the basolateral membrane of intestinal epithelial cells (IECs). Enterocyte-specific Zip14 ablation (Zip14ΔIEC) in mice was developed to study the functions of this transporter in enterocytes. This gene deletion led to increased intestinal permeability, increased IL-6 and IFNγ expression, mild endotoxemia, and intestinal dysbiosis. RNA sequencing was used for transcriptome profiling. These analyses revealed differential expression of specific intestinal proinflammatory and tight junction (TJ) genes. Binding of transcription factors, including NF-κβ, STAT3, and CDX2, to appropriate promoter sites of these genes supports the differential expression shown with chromatin immunoprecipitation assays. Total histone deacetylase (HDAC), and specifically HDAC3, activities were markedly reduced with Zip14 ablation. Intestinal organoids derived from ΔIEC mice display TJ and cytokine gene dysregulation compared with control mice. Differential expression of specific genes was reversed with zinc supplementation of the organoids. We conclude that zinc-dependent HDAC enzymes acquire zinc ions via Zip14-mediated transport and that intestinal integrity is controlled in part through epigenetic modifications.NEW & NOTEWORTHY We show that enterocyte-specific ablation of zinc transporter Zip14 (Slc39a14) results in selective dysbiosis and differential expression of tight junction proteins, claudin 1 and 2, and specific cytokines associated with intestinal inflammation. HDAC activity and zinc uptake are reduced with Zip14 ablation. Using intestinal organoids, the expression defects of claudin 1 and 2 are resolved through zinc supplementation. These novel results suggest that zinc, an essential micronutrient, influences gene expression through epigenetic mechanisms.