Inflammatory bowel disease (IBD) can be caused by a variety of factors, including hereditary and environmental influences, that lead to dysfunction of the intestinal immune system. Mesenchymal stem cells (MSCs) exhibit important regulatory roles in relieving inflammation and repairing damaged tissues. Although neutrophils are important participants in the development of inflammatory reactions, they are also essential for maintaining intestinal balance during the process of mitigation of IBD by MSCs. Here, we constructed a dextran sulfate sodium (DSS)-induced mouse IBD model and evaluated the effects of treatment with human umbilical cord MSCs. Mouse body weight, faecal traits, colon/spleen gross morphology, tissue histology and immunohistochemical staining, and inflammatory factors were analysed. Magnetic beads were used to sort infiltrating neutrophils from intestinal tissues, and their phenotypes were identified. The neutrophil inflammatory environment was also simulated in vitro, and signalling pathways involved in MSC regulation of neutrophil phenotype were analysed. Human umbilical cord MSCs effectively alleviated DSS-induced weight loss, colon shortening, and intestinal mucosal injury, and reduced clinical disease activity index. The number of neutrophils that infiltrated the intestines of mice treated with human umbilical cord MSCs were decreased and polarised toward the N2 phenotype; at the same time, ERK phosphorylation was inhibited. In vitro experiments showed that addition of the ERK phosphorylation inhibitor, PD98059, down-regulated the expression of N1 neutrophils, while up-regulating that of N2 neutrophils. The colon tissues from patients with IBD were infiltrated with neutrophils. Further, relative to healthy controls, the markers of N1 neutrophils (ICAM-1, FAS, and CCL3) were highly expressed in colon tissues from patients with IBD, whereas the markers of N2 neutrophils (VEGF, CCL2, and CXCR4) were almost undetectable. In conclusion, during alleviation of IBD, human umbilical cord MSCs polarise neutrophils toward the “N2” phenotype by inhibiting activation of ERK signalling.

中文翻译：

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人脐带间充质干细胞通过抑制中性粒细胞的ERK磷酸化来减轻炎症性肠病。

炎症性肠病（IBD）可由多种因素引起，包括遗传和环境影响，这些因素会导致肠道免疫系统功能障碍。间充质干细胞（MSC）在缓解炎症和修复受损组织方面显示出重要的调节作用。尽管中性粒细胞是炎症反应发展的重要参与者，但它们对于在MSC缓解IBD的过程中维持肠道平衡也是必不可少的。在这里，我们构建了硫酸右旋糖酐钠（DSS）诱导的小鼠IBD模型，并评估了人脐带MSC治疗的效果。分析小鼠体重，粪便性状，结肠/脾大体形态，组织组织学和免疫组化染色以及炎性因子。磁珠用于分类从肠组织浸润的中性粒细胞，并鉴定其表型。还体外模拟了中性粒细胞的炎性环境，并分析了涉及MSC调节中性粒细胞表型的信号传导途径。人脐带间充质干细胞可有效减轻DSS引起的体重减轻，结肠缩短和肠粘膜损伤，并降低临床疾病活动指数。浸润了人脐带间充质干细胞的小鼠肠道中性粒细胞的数量减少，并向N2型极化。同时，ERK的磷酸化受到抑制。体外实验表明，加入ERK磷酸化抑制剂PD98059下调N1中性粒细胞的表达，同时上调N2中性粒细胞的表达。IBD患者的结肠组织被嗜中性粒细胞浸润。此外，相对于健康对照组，IBD患者结肠组织中N1中性粒细胞的标志物（ICAM-1，FAS和CCL3）高表达，而N2中性粒细胞的标志物（VEGF，CCL2和CXCR4）几乎无法检测到。 。总之，在减轻IBD的过程中，人脐带间充质干细胞通过抑制ERK信号的激活使嗜中性粒细胞向“ N2”表型极化。