Ileitis-associated tertiary lymphoid organs arise at lymphatic valves and impede mesenteric lymph flow in response to tumor necrosis factor.
Ileitis-associated tertiary lymphoid organs arise at lymphatic valves and impede mesenteric lymph flow in response to tumor necrosis factor.
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DOI：
10.1016/j.immuni.2021.10.003
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发表时间：
2021-12-14
期刊：
影响因子：
32.4
通讯作者：
Randolph GJ
中科院分区：
文献类型：
--
作者：
Czepielewski RS;Erlich EC;Onufer EJ;Young S;Saunders BT;Han YH;Wohltmann M;Wang PL;Kim KW;Kumar S;Hsieh CS;Scallan JP;Yang Y;Zinselmeyer BH;Davis MJ;Randolph GJ
肠系膜的淋巴管炎和三级淋巴器官（TLOs）的形成是克罗恩病的特征。在这里，我们研究了这些TLOs的起源及其对疾病进展的影响。对TNFΔARE小鼠（一种回肠炎模型）回肠和回肠引流集淋巴管（clv）引流至肠系膜淋巴结的全载和活体成像显示，clv瓣膜处形成TLOs。TLOs阻碍了细胞和分子从肠道流出，是淋巴渗漏和回流的部位。TNF中和开始于TLO形成的早期阶段，恢复淋巴运输。然而，在肿瘤坏死因子中和后，慢性TLOs强烈发展，抵抗血流的回归和恢复。TNF刺激培养淋巴内皮细胞对振荡剪切应力的重编程反应，阻止了瓣膜相关基因的诱导。由瓣膜完整性丧失和TLOs形成驱动的免疫细胞运输中断可能导致克罗恩病的病理。淋巴管炎和肠系膜三级淋巴器官（TLOs）的形成是克罗恩病的特征。czepelewski等人发现，细胞因子TNF驱动瓣膜完整性的丧失和TLO的形成，从而破坏了克罗恩样回肠炎模型中的淋巴运输。由此导致的免疫细胞运输障碍可能导致克罗恩病的病理。
Lymphangitis and the formation of tertiary lymphoid organs (TLOs) in the mesentery are features of Crohn’s disease. Here we examined the genesis of these TLOs and their impact on disease progression. Whole-mount and intravital imaging of the ileum and ileum-draining collecting lymphatic vessels (CLVs) draining to mesenteric lymph nodes from TNFΔARE mice, a model of ileitis, revealed TLOs formation at valves of CLVs. TLOs obstructed cellular and molecular outflow from the gut, and were sites of lymph leakage and backflow. TNF neutralization begun at early stages of TLO formation restored lymph transport. However, robustly developed, chronic TLOs resisted regression and restoration of flow after TNF neutralization. TNF stimulation of cultured lymphatic endothelial cells reprogrammed responses to oscillatory shear stress, preventing induction of valve-associated genes. Disrupted transport of immune cells driven by loss of valve integrity and TLOs formation may contribute to the pathology of Crohn’s disease. Lymphangitis and the formation of mesenteric tertiary lymphoid organs (TLOs) are features of Crohn’s disease. Czepielewski et al. find that the cytokine TNF drives loss of valve integrity and TLO formation, thereby disrupting lymphatic transport in a model of Crohn’s like-ileitis. The resulting impairment of immune cell transport may contribute to the pathology of Crohn’s disease.
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影响因子：
4.6
作者：
Gossa S;Nayak D;Zinselmeyer BH;McGavern DB
通讯作者：
McGavern DB
DOI：
10.1084/jem.185.9.1573
发表时间：
1997-05-05
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Cope AP;Liblau RS;Yang XD;Congia M;Laudanna C;Schreiber RD;Probert L;Kollias G;McDevitt HO
通讯作者：
McDevitt HO
影响因子：
64.8
作者：
Esterhazy, Daria;Canesso, Maria C. C.;Mucida, Daniel
通讯作者：
Mucida, Daniel
影响因子：
10.5
作者：
Cha B;Geng X;Mahamud MR;Fu J;Mukherjee A;Kim Y;Jho EH;Kim TH;Kahn ML;Xia L;Dixon JB;Chen H;Srinivasan RS
通讯作者：
Srinivasan RS
DOI：
10.1038/s41575-020-0354-0
发表时间：
2020-12
期刊：
Nature reviews. Gastroenterology & hepatology
影响因子：
--
作者：
Goodman WA;Erkkila IP;Pizarro TT
通讯作者：
Pizarro TT