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神经炎症中的脑膜淋巴管血管系统。

The meningeal lymphatic vasculature in neuroinflammation.

机构信息

Lymphatic Vasculature and Inflammation Research Laboratory, Facultad de Ciencias de la Salud, Instituto de Ciencias Biomédicas, Universidad Autónoma de Chile, Talca, Chile.

Escuela de Diseño, Duoc UC, Viña del Mar, Chile.

出版信息

FASEB J. 2022 May;36(5):e22276. doi: 10.1096/fj.202101574RR.

Abstract

The lymphatic vasculature is a unidirectional network of lymphatic endothelial cells, whose main role is to maintain fluid homeostasis along with the absorption of dietary fat in the gastrointestinal organs and management and coordination of immune cell trafficking into lymph nodes during homeostasis and under inflammatory conditions. In homeostatic conditions, immune cells, such as dendritic cells, macrophages, or T cells can enter into the lymphatic vasculature and move easily through the lymph reaching secondary lymph nodes where immune cell activation or peripheral tolerance can be modulated. However, under inflammatory conditions such as pathogen infection, increased permeabilization of lymphatic vessels allows faster immune cell migration into inflamed tissues following a chemokine gradient, facilitating pathogen clearance and the resolution of inflammation. Interestingly, since the re-discovery of lymphatic vasculature in the central nervous system, known as the meningeal lymphatic vasculature, the role of these lymphatics as a key player in several neurological disorders has been described, with emphasis on the neurodegenerative process. Alternatively, less has been discussed about meningeal lymphatics and its role in neuroinflammation. In this review, we discuss current knowledge about the anatomy and function of the meningeal lymphatic vasculature and specifically analyze its contribution to different neuroinflammatory processes, highlighting the potential therapeutic target of meningeal lymphatic vasculature in these pathological conditions.

摘要

淋巴血管系统是一个单向的淋巴管内皮细胞网络,其主要作用是在胃肠道器官中维持液体平衡,吸收膳食脂肪,并在稳态和炎症条件下管理和协调免疫细胞向淋巴结的迁移。在稳态条件下,免疫细胞,如树突状细胞、巨噬细胞或 T 细胞,可以进入淋巴管,并通过淋巴轻松移动,到达二级淋巴结,在那里可以调节免疫细胞的激活或外周耐受。然而,在病原体感染等炎症条件下,淋巴管的通透性增加,使得免疫细胞能够沿着趋化因子梯度更快地迁移到炎症组织中,促进病原体清除和炎症的解决。有趣的是,自从中央神经系统(脑膜)中的淋巴血管系统被重新发现以来,这些淋巴管作为几种神经疾病的关键参与者的作用已经被描述,重点是神经退行性过程。另一方面,脑膜淋巴管及其在神经炎症中的作用讨论得较少。在这篇综述中,我们讨论了脑膜淋巴血管系统的解剖和功能的现有知识,并特别分析了其对不同神经炎症过程的贡献,强调了脑膜淋巴血管系统在这些病理条件下作为潜在治疗靶点的重要性。

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