TNFΔARE Mice Display Abnormal Lymphatics and Develop Tertiary Lymphoid Organs in the Mesentery.
TNFΔARE Mice Display Abnormal Lymphatics and Develop Tertiary Lymphoid Organs in the Mesentery.
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DOI：
10.1016/j.ajpath.2016.12.007
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发表时间：
2017-04
期刊：
影响因子：
--
通讯作者：
Sonia Rehal;P. von der Weid
中科院分区：
文献类型：
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作者：
Sonia Rehal;P. von der Weid
慢性炎症性疾病与对环境抗原的持续和增强的反应有关。作为对这种过度免疫状态的适应性反应，受影响的组织通常发育三级淋巴器官。克罗恩病（CD）是一种肠道慢性炎症性疾病，对其研究报告了粘膜壁内存在三级淋巴器官，沿着其他淋巴疾病，如淋巴管生成和淋巴管阻塞。这些观察结果表明，下游肠系膜淋巴管和淋巴引流到肠系膜淋巴结可能会受到影响。然而，目前尚缺乏关于CD肠系膜血管的形态学特征和功能状态的信息。利用共聚焦成像、PCR、流式细胞术和功能策略，我们在已建立的TNF Δ ARE小鼠CD模型中解决了这些问题，并发现该小鼠模型具有许多类似于人CD的淋巴异常。这些异常包括肠淋巴管扩张、肠系膜淋巴结淋巴结病和肠系膜和粘膜中的淋巴管生成。重要的是，TNFΔ ARE小鼠还存在肠系膜三级淋巴器官，并改变了树突状细胞向肠系膜淋巴结的淋巴转运，这两个特征可能积极调节免疫。我们的研究结果为TNF Δ ARE小鼠模型中的淋巴重建提供了关键的见解。他们阐明了这些淋巴变化参与CD中观察到的免疫功能障碍，并建议淋巴系统作为治疗选择的新靶点。
Chronic inflammatory diseases are associated with a persistent and enhanced response to environmental antigens. As an adaptive response to this exaggerated immune state, affected tissue typically develops tertiary lymphoid organs. Studies of Crohn disease (CD), a chronic inflammatory disease of the intestinal tract, report tertiary lymphoid organs present within the mucosal wall, along with other lymphatic diseases, such as lymphangiogenesis and obstructed lymphatic vessels. These observations suggest that downstream mesenteric lymphatic vessels and lymph drainage into mesenteric lymph nodes may be compromised. However, information is lacking on the morphologic features and functional status of mesenteric lymphatics in CD. Using confocal imaging, PCR, flow cytometry, and functional strategies, we addressed these questions in the establishedTNFΔAREmouse model of CD and found that this mouse model had many lymphatic abnormalities reminiscent of human CD. These abnormalities include intestinal lymphangiectasia, mesenteric lymph node lymphadenopathy, and lymphangiogenesis in both the mesentery and mucosa. Critically,TNFΔAREmice also present mesenteric tertiary lymphoid organs and have altered lymphatic transport of dendritic cells to mesenteric lymph nodes, two features likely to actively modulate immunity. Our findings provide key insights into lymphatic remodeling in theTNFΔAREmouse model. They shed light on the involvement of these lymphatic changes in immune dysfunctions observed in CD and suggest the lymphatic system as new target for therapeutic options.