Inflammation Research Network and Smooth Muscle Research Group, Snyder Institute for Chronic Diseases, Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary , Calgary, Alberta , Canada.
Am J Physiol Gastrointest Liver Physiol. 2018 Mar 1;314(3):G408-G417. doi: 10.1152/ajpgi.00340.2017. Epub 2017 Dec 14.
Inflammatory bowel disease (IBD) has a complex pathophysiology with limited treatments. Structural and functional changes in the intestinal lymphatic system have been associated with the disease, with increased risk of IBD occurrence linked to a history of acute intestinal injury. To examine the potential role of the lymphatic system in inflammation recurrence, we evaluated morphological and functional changes in mouse mucosal and mesenteric lymphatic vessels, and within the mesenteric lymph nodes during acute ileitis caused by a 7-day treatment with dextran sodium sulfate (DSS). We monitored whether the changes persisted during a 14-day recovery period and determined their potential consequences on dendritic cell (DC) trafficking between the mucosa and lymphoid tissues. DSS administration was associated with marked lymphatic abnormalities and dysfunctions exemplified by lymphangiectasia and lymphangiogenesis in the ileal mucosa and mesentery, increased mesenteric lymphatic vessel leakage, and lymphadenopathy. Lymphangiogenesis and lymphadenopathy were still evident after recovery from intestinal inflammation and correlated with higher numbers of DCs in mucosal and lymphatic tissues. Specifically, a deficit in CD103 DCs observed during acute DSS in the lamina propria was reversed and further enhanced during recovery. We concluded that an acute intestinal insult caused alterations of the mesenteric lymphatic system, including lymphangiogenesis, which persisted after resolution of inflammation. These morphological and functional changes could compromise DC function and movement, increasing susceptibility to further gastrointestinal disease. Elucidation of the changes in mesenteric and intestinal lymphatic function should offer key insights for new therapeutic strategies in gastrointestinal disorders such as IBD. NEW & NOTEWORTHY Lymphatic integrity plays a critical role in small intestinal homeostasis. Acute intestinal insult in a mouse model of acute ileitis causes morphological and functional changes in mesenteric and intestinal lymphatic vessels. While some of the changes significantly regressed during inflammation resolution, others persisted, including lymphangiogenesis and altered dendritic cell function and movement, potentially increasing susceptibility to the recurrence of gastrointestinal inflammation.
炎症性肠病（IBD）的发病机制复杂，治疗方法有限。肠道淋巴系统的结构和功能变化与该疾病有关，IBD 的发生风险与急性肠道损伤史相关。为了研究淋巴系统在炎症复发中的潜在作用，我们评估了在葡聚糖硫酸钠（DSS）诱导的 7 天急性回肠炎小鼠模型中，肠道黏膜和肠系膜淋巴管以及肠系膜淋巴结中的形态和功能变化。我们监测了这些变化在 14 天恢复期是否持续，并确定了它们对黏膜和淋巴组织之间树突状细胞（DC）迁移的潜在影响。DSS 处理与明显的淋巴异常和功能障碍相关，例如回肠黏膜和肠系膜的淋巴管扩张和新生、肠系膜淋巴管渗漏增加以及淋巴结病。在肠道炎症恢复后，仍然存在淋巴管扩张和淋巴结病，并且与黏膜和淋巴组织中更多的 DC 相关。具体而言，在急性 DSS 期间固有层中观察到的 CD103 DC 缺陷在恢复期间得到逆转并进一步增强。我们得出结论，急性肠道损伤导致肠系膜淋巴系统发生改变，包括淋巴管扩张，这些改变在炎症消退后仍然存在。这些形态和功能的改变可能会影响 DC 的功能和迁移，增加对进一步胃肠道疾病的易感性。阐明肠系膜和肠道淋巴管功能的变化，应为 IBD 等胃肠道疾病的新治疗策略提供关键见解。新的和值得注意的是，淋巴完整性在小肠稳态中起着关键作用。急性回肠炎小鼠模型中的急性肠道损伤导致肠系膜和肠道淋巴管的形态和功能发生变化。虽然一些变化在炎症消退过程中显著消退，但其他变化仍持续存在，包括淋巴管扩张以及改变的树突状细胞功能和迁移，这可能会增加胃肠道炎症复发的易感性。
