美国华盛顿大学医学院Gwendalyn J. Randolph研究团队发现，回肠炎相关的三级淋巴器官出现在淋巴管瓣并阻碍肠系膜淋巴流动以响应肿瘤坏死因子（TNF）。2021年11月16日，国际知名学术期刊《免疫》在线发表了这一成果。

研究人员报道了三级淋巴器官（TLO）的起源及其对疾病进展的影响。对TNF^ΔARE小鼠的回肠和回肠引流到肠系膜淋巴结的集合淋巴管（CLV）进行了整体标本和活体成像，显示了CLV瓣膜处的TLO形成。TLO阻碍了细胞和分子从肠道流出，并且是淋巴渗漏和倒流的场所。在TLO形成的早期阶段开始的TNF中和恢复了淋巴运输。

然而，在TNF中和后，发育良好的慢性TLO抵抗退化和恢复流动。TNF对培养的淋巴内皮细胞的刺激重塑了对振荡剪切应力的反应，从而阻止了对瓣膜相关基因的诱导。在瓣膜完整性丧失和TLO形成的驱动下，免疫细胞的运输中断，这可能有助于克罗恩病的病理。

据悉，淋巴结炎和肠系膜中TLO的形成是克罗恩病的特征。

附：英文原文

Title: Ileitis-associated tertiary lymphoid organs arise at lymphatic valves and impede mesenteric lymph flow in response to tumor necrosis factor

Author: Rafael S. Czepielewski, Emma C. Erlich, Emily J. Onufer, Shannon Young, Brian T. Saunders, Yong-Hyun Han, Mary Wohltmann, Peter L. Wang, Ki-Wook Kim, Shashi Kumar, Chyi-Song Hsieh, Joshua P. Scallan, Ying Yang, Bernd H. Zinselmeyer, Michael J. Davis, Gwendalyn J. Randolph

Issue&Volume: 2021-11-16

Abstract: Lymphangitis and the formation of tertiary lymphoid organs (TLOs) in the mesenteryare features of Crohn’s disease. Here, we examined the genesis of these TLOs and theirimpact on disease progression. Whole-mount and intravital imaging of the ileum andileum-draining collecting lymphatic vessels (CLVs) draining to mesenteric lymph nodesfrom TNFΔARE mice, a model of ileitis, revealed TLO formation at valves of CLVs. TLOs obstructedcellular and molecular outflow from the gut and were sites of lymph leakage and backflow.Tumor necrosis factor (TNF) neutralization begun at early stages of TLO formationrestored lymph transport. However, robustly developed, chronic TLOs resisted regressionand restoration of flow after TNF neutralization. TNF stimulation of cultured lymphaticendothelial cells reprogrammed responses to oscillatory shear stress, preventing theinduction of valve-associated genes. Disrupted transport of immune cells, driven byloss of valve integrity and TLO formation, may contribute to the pathology of Crohn’sdisease.

DOI: 10.1016/j.immuni.2021.10.003

Source: https://www.cell.com/immunity/fulltext/S1074-7613(21)00409-X