The lymphatic system is essential for lipid absorption/transport from the digestive system, maintenance of tissue fluid and protein homeostasis, and immune surveillance. Despite recent progress toward understanding the cellular and molecular mechanisms underlying the formation of the lymphatic vascular system, the nature of lymphatic vessel abnormalities and disease in humans is complex and poorly understood. The mature lymphatic vasculature forms a hierarchical network in which lymphatic endothelial cells (LECs) are joined by functionally specialized cell-cell junctions to maintain the integrity of lymphatic vessels. Blind-ended and highly permeable lymphatic capillaries drain interstitial fluid via discontinuous, button-like LEC junctions, whereas collecting lymphatic vessels, surrounded by intact basement membranes and lymphatic smooth muscle cells, have continuous, zipper-like LEC junctions to transport lymph to the blood circulatory system without leakage. In this review, we discuss the recent advances in our understanding of the mechanisms by which lymphatic button- and zipper-like junctions play critical roles in lymphatic permeability and function in a tissue- and organ-specific manner, including lacteals of the small intestine. We also provide current knowledge related to key pathways and factors such as VEGF and RhoA/ROCK signaling that control lymphatic endothelial cell junctional integrity.

淋巴系统对于脂质从消化系统吸收/转运，维持组织液和蛋白质稳态以及免疫监视至关重要。尽管最近在理解构成淋巴管系统形成的细胞和分子机制方面取得了进展，但是人类淋巴管异常和疾病的性质仍然是复杂且知之甚少的。成熟的淋巴管系统形成一个层次网络，其中淋巴管内皮细胞（LEC）通过功能性专门化的细胞-细胞连接处相连，以维持淋巴管的完整性。盲端和高渗透性的淋巴毛细血管通过不连续的纽扣状LEC连接排出组织液，而收集淋巴管，被完整的基底膜和淋巴平滑肌细胞所围绕，具有连续的拉链状LEC连接，可将淋巴输送至血液循环系统而无渗漏。在这篇综述中，我们讨论了我们对淋巴纽扣状和拉链状连接以组织和器官特异性方式（包括小肠的乳腺）在淋巴通透性和功能中起关键作用的机制的理解的最新进展。我们还提供与关键途径和因素有关的当前知识，例如控制淋巴管内皮细胞连接完整性的VEGF和RhoA / ROCK信号传导。我们讨论我们对机制的了解，其中淋巴纽扣状和拉链状连接在组织和器官特异性方式（包括小肠的乳腺）中在淋巴通透性和功能中起关键作用的机理的最新进展。我们还提供与关键途径和因素有关的当前知识，例如控制淋巴管内皮细胞连接完整性的VEGF和RhoA / ROCK信号传导。我们讨论了我们对机制的了解，其中淋巴纽扣状和拉链状连接在组织和器官特异性方式（包括小肠的乳腺）中在淋巴通透性和功能中起着关键作用，我们对这些机制的理解进行了讨论。我们还提供与关键途径和因素有关的当前知识，例如控制淋巴管内皮细胞连接完整性的VEGF和RhoA / ROCK信号传导。