Department of Microbiology and Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
Department of Otorhinolaryngology-Head and Neck Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
Genes Cells. 2023 Nov;28(11):776-788. doi: 10.1111/gtc.13065. Epub 2023 Sep 7.
In the intestine, interleukin (IL)-23 and IL-22 from immune cells in the lamina propria contribute to maintenance of the gut epithelial barrier through the induction of antimicrobial production and the promotion of epithelial cell proliferation. Several previous studies suggested that some of the functions of the IL-23/IL-22 axis on intestinal epithelial cells are shared between the small and large intestines. However, the similarities and differences of the IL-23/IL-22 axis on epithelial cells between these two anatomical sites remain unclear. Here, we comprehensively analyzed the gene expression of intestinal epithelial cells in the ileum and colon of germ-free, Il23 , and Il22 mice by RNA-sequencing. We found that while the IL-23/IL-22 axis is largely dependent on gut microbiota in the small intestine, it is much less dependent on it in the large intestine. In addition, the negative regulation of lipid metabolism in the epithelial cells by IL-23 and IL-22 in the small intestine was revealed, whereas the positive regulation of epithelial cell proliferation by IL-23 and IL-22 in the large intestine was highlighted. These findings shed light on the intestinal site-specific role of the IL-23/IL-22 axis in maintaining the physiological functions of intestinal epithelial cells.
在肠道中，固有层中的免疫细胞产生的白细胞介素 (IL)-23 和 IL-22 通过诱导抗菌产物的产生和促进上皮细胞增殖来维持肠道上皮屏障。先前的几项研究表明，IL-23/IL-22 轴在肠道上皮细胞上的一些功能在小肠和大肠之间是共享的。然而，IL-23/IL-22 轴在上皮细胞上在这两个解剖部位之间的相似性和差异性仍不清楚。在这里，我们通过 RNA 测序全面分析了无菌、Il23 和 Il22 小鼠回肠和结肠的肠道上皮细胞的基因表达。我们发现，虽然 IL-23/IL-22 轴在小肠中在很大程度上依赖于肠道微生物群，但在大肠中则依赖程度较低。此外，揭示了 IL-23 和 IL-22 在小肠中对上皮细胞脂质代谢的负向调节，而 IL-23 和 IL-22 在大肠中对上皮细胞增殖的正向调节则被强调。这些发现揭示了 IL-23/IL-22 轴在维持肠道上皮细胞生理功能方面的肠道部位特异性作用。
