Roles of organ-specific lymphatic vessels Lymphatic vessels are spread throughout the human body and have critical functions in mammalian physiology. Petrova et al. review emerging roles of the lymphatic vasculature in organ function and pathology and provide perspectives beyond the traditional view of lymphatic vessels in the maintenance of fluid homeostasis. The authors highlight new insights into lymphatic vessel function and lymphatic endothelial cell biology as it relates to intestinal lacteals, lymph nodes, central nervous system meninges, and cancer. Recent steps toward therapeutic opportunities that could alter lymphatic function or growth are also discussed. Science, this issue p. eaax4063 BACKGROUND Blood and lymphatic vessel networks form two arms of the vertebrate cardiovascular system that play complementary roles in body homeostasis maintenance and multiple diseases. Lymphatic vessels are lined with lymphatic endothelial cells (LECs), which represent a distinct endothelial cell lineage characterized by a specific transcriptional and metabolic program. The general functions of lymphatic vessels in fluid transport and immunosurveillance are well recognized, as is their specialization into capillaries, serving as an entrance point of interstitial components and immune cells and collecting vessels that deliver lymph to lymph nodes (LNs) and blood circulation. It is becoming increasingly clear that adult lymphatic vessels, exposed to different organ-specific environments, acquire distinct characteristics and in turn execute multiple tissue-specific functions. ADVANCES This Review provides an overview of the recent advances in our understanding of new functions of adult mammalian lymphatic vessels, such as immunomodulation, contribution to neurodegenerative and neuroinflammatory diseases, and response to anticancer therapies. LN LECs have been shown to archive antigens and directly regulate immune cell properties, including immune cell survival and positioning within the LN. Rediscovery of meningeal lymphatic vessels has uprooted the dogma of brain immune privilege, and these vessels now emerge as key regulators of neuroinflammation and neurodegeneration. Intestinal lacteals display distinct cellular characteristics that make them especially suitable for dietary fat uptake and designate them as promising targets for the treatment of obesity. Tumor lymphatics have long been recognized as conduits for metastatic cell dissemination; however, recent data show that lymphatic vessels have multiple additional functions, such as forming metastatic cancer cell niches but also controlling productive response to antitumor immune therapies. Last, discovery of vascular beds with hybrid blood and lymphatic characteristics, such as the Schlemm’s canal in the eye and the kidney ascending vasa recta, underscores the degree and potential of endothelial cell plasticity. OUTLOOK Molecular characteristics of organ-specific vascular beds and understanding their organotypic functions are among the current fundamental questions of vascular biology. Emerging evidence points to the major contribution of lymphatic vessels, a vascular system generally associated only with tissue-drainage functions. High-resolution analyses of endothelial heterogeneity and organotypic lymphatic vessel architecture, in addition to deciphering the molecular codes that LECs use for communication with other cell types, are necessary to fully understand the role of lymphatics in organ physiology and pathology. Integration of such knowledge with research from other fields, such as immunology and bioengineering, will uncover new possibilities for promoting tissue regeneration and developing new therapies for cancer, obesity, neuroinflammation, and neurodegeneration. Organ-specific lymphatic vessels in small intestine, meninges, and LN. (Left) Small intestine. Shown are LYVE-1+ (green) lacteal, CD31+(red) capillary plexus, and α-smooth actin+ (blue) longitudinal smooth muscle cells. (Middle) Meninges. Shown are LYVE-1+ (green) and VEGFR3+ (blue) lymphatic vessels and CD31+ (red) blood vessels. (Right) LN. Shown are LYVE-1+ (green) lymphatic vessels and CD31+(red) blood vessels, including high endothelial venules. IMAGES: J. BERNIER-LATMANI AND H. CHO The general functions of lymphatic vessels in fluid transport and immunosurveillance are well recognized. However, accumulating evidence indicates that lymphatic vessels play active and versatile roles in a tissue- and organ-specific manner during homeostasis and in multiple disease processes. This Review discusses recent advances to understand previously unidentified functions of adult mammalian lymphatic vessels, including immunosurveillance and immunomodulation upon pathogen invasion, transport of dietary fat, drainage of cerebrospinal fluid and aqueous humor, possible contributions toward neurodegenerative and neuroinflammatory diseases, and response to anticancer therapies.

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淋巴管的生物学功能

器官特异性淋巴管的作用 淋巴管遍布人体，在哺乳动物生理学中具有重要功能。彼得罗娃等人。回顾淋巴管系统在器官功能和病理学中的新作用，并提供超越传统观点的淋巴管在维持体液稳态方面的观点。作者强调了对淋巴管功能和淋巴管内皮细胞生物学的新见解，因为它与肠道乳糜泻、淋巴结、中枢神经系统脑膜和癌症有关。还讨论了最近采取的可能改变淋巴功能或生长的治疗机会的步骤。科学，这个问题 p。eaax4063 背景血液和淋巴管网络形成脊椎动物心血管系统的两个臂，它们在身体稳态维持和多种疾病中发挥互补作用。淋巴管内衬淋巴管内皮细胞 (LEC)，它代表了一种独特的内皮细胞谱系，其特征是特定的转录和代谢程序。淋巴管在液体运输和免疫监视中的一般功能是众所周知的，它们专门化为毛细血管，作为间质成分和免疫细胞的入口点，以及将淋巴输送到淋巴结 (LN) 和血液循环的收集血管。越来越清楚的是，暴露于不同器官特异性环境的成人淋巴管，获得不同的特征，进而执行多种组织特异性功能。进展 本综述概述了我们对成年哺乳动物淋巴管新功能的理解的最新进展，例如免疫调节、对神经退行性疾病和神经炎症疾病的贡献以及对抗癌疗法的反应。LN LEC 已被证明可以存档抗原并直接调节免疫细胞特性，包括免疫细胞在 LN 内的存活和定位。脑膜淋巴管的重新发现已经根除脑免疫特权的教条，这些血管现在成为神经炎症和神经变性的关键调节剂。肠道乳酸显示出独特的细胞特征，使它们特别适合膳食脂肪摄取，并将其指定为治疗肥胖症的有希望的靶点。长期以来，肿瘤淋巴管被认为是转移性细胞传播的管道。然而，最近的数据表明，淋巴管具有多种附加功能，例如形成转移性癌细胞壁龛，还控制对抗肿瘤免疫疗法的生产反应。最后，发现具有混合血液和淋巴特征的血管床，例如眼中的施累姆氏管和肾上行血管，强调了内皮细胞可塑性的程度和潜力。展望器官特异性血管床的分子特征及其器官功能是当前血管生物学的基本问题之一。新出现的证据表明淋巴管的主要贡献，这是一种通常仅与组织引流功能相关的血管系统。对内皮异质性和器官型淋巴管结构的高分辨率分析，除了破译 LEC 用于与其他细胞类型通信的分子代码外，对于充分了解淋巴管在器官生理学和病理学中的作用也是必要的。将这些知识与免疫学和生物工程等其他领域的研究相结合，将为促进组织再生和开发针对癌症、肥胖症、神经炎症、和神经变性。小肠、脑膜和 LN 中的器官特异性淋巴管。（左）小肠。显示的是 LYVE-1+（绿色）乳状细胞、CD31+（红色）毛细血管丛和 α-平滑肌动蛋白+（蓝色）纵向平滑肌细胞。（中）脑膜。显示的是 LYVE-1+（绿色）和 VEGFR3+（蓝色）淋巴管以及 CD31+（红色）血管。（右）LN。显示的是 LYVE-1+（绿色）淋巴管和 CD31+（红色）血管，包括高内皮小静脉。图像：J. BERNIER-LATMANI 和 H. CHO 淋巴管在液体运输和免疫监视中的一般功能已得到广泛认可。然而，越来越多的证据表明，淋巴管在体内平衡和多种疾病过程中以组织和器官特异性方式发挥着积极和多功能的作用。