Brice Daniel P, Murray Graeme I, Wilson Heather M, Porter Ross J, Berry Susan, Durum Scott K, McLean Mairi H
School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen AB25 2ZD, UK.
Centre for Inflammation Research, Queens Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, UK.
Biology (Basel). 2022 Mar 11;11(3):427. doi: 10.3390/biology11030427.
A treatment with direct healing effects on the gastrointestinal epithelial barrier is desirable for inflammatory bowel disease (IBD). Interleukin-27 (IL-27) is an immunoregulatory cytokine, and oral delivery is an effective treatment in murine models of IBD. We aimed to define IL-27 effects on the human gastrointestinal epithelial barrier. We characterised gene and protein expression of permeability mediators in a human colon-derived organoid model. Functional permeability was determined in an organoid-derived 2D monolayer by transepithelial electrical resistance. IL-27 effects on epithelial innate immune responses were assessed through expression of cytokines, anti-microbial peptides and MUC genes. IL-27 effects on wound healing and proliferation were determined in human colon epithelial cell lines. IL-27 led to restoration of permeability regulation following inflammatory cytokine insult (p = 0.001), associated with differential expression of tight junction mediators with decrease in claudin 2 (p = 0.024) and increase in claudin 4 (p < 0.001), E-cadherin (p < 0.001) and zona occludens (p = 0.0014). IL-27 evoked differential gene expression of epithelial-derived innate immune responses (reduced IL1B and IL18, and increased IL33, HBD1, MUC1 and MUC2; p < 0.012). IL-27 induced epithelial barrier wound healing through restitution (p < 0.001), and increased proliferation (p < 0.001) following injury. Overall, IL-27 provokes mucosal healing of the human gastrointestinal epithelial barrier.
对于炎症性肠病（IBD）而言，一种对胃肠道上皮屏障具有直接愈合作用的治疗方法是很有必要的。白细胞介素-27（IL-27）是一种免疫调节细胞因子，口服给药在IBD小鼠模型中是一种有效的治疗方法。我们旨在确定IL-27对人胃肠道上皮屏障的作用。我们在人结肠来源的类器官模型中对通透性介质的基因和蛋白表达进行了表征。通过跨上皮电阻在类器官来源的二维单层中测定功能通透性。通过细胞因子、抗菌肽和MUC基因的表达评估IL-27对上皮固有免疫反应的影响。在人结肠上皮细胞系中确定IL-27对伤口愈合和增殖的影响。IL-27导致炎症细胞因子损伤后通透性调节的恢复（p = 0.001），这与紧密连接介质的差异表达相关，claudin 2减少（p = 0.024），claudin 4增加（p < 0.001）、E-钙黏蛋白（p < 0.001）和闭合蛋白（p = 0.0014）。IL-27引起上皮来源的固有免疫反应的差异基因表达（IL1B和IL18减少，IL33、HBD1、MUC1和MUC2增加；p < 0.012）。IL-27通过修复诱导上皮屏障伤口愈合（p < 0.001），并在损伤后增加增殖（p < 0.001）。总体而言，IL-27可促进人胃肠道上皮屏障的黏膜愈合。
