Department of Physiology, Semmelweis University School of Medicine, Budapest, Hungary.
MTA-SE "Lendület" Lymphatic Physiology Research Group, Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary.
Front Immunol. 2020 Jan 14;10:3043. doi: 10.3389/fimmu.2019.03043. eCollection 2019.
Recently, the presence of lymphatics has been demonstrated and characterized in the dura mater, which is in contrast to the well-accepted view indicating the lack of a classical lymphatic drainage system of the central nervous system (CNS). Moreover, the role of meningeal lymphatics in the pathogenesis of Alzheimer's disease and multiple sclerosis was suggested. However, the possible regulators of the developmental program and function of meningeal lymphatics remain unclear. Here, we aimed at characterizing the lymph flow dependence of the developmental program and function of the meningeal lymphatics. First, we demonstrated that lymphatics present in the dura mater are involved in the uptake and transport of macromolecules from the CNS. Meningeal lymphatics develop during the postnatal period which process involves the maturation of the vessels. The formation of mature meningeal lymphatics coincides with the increase of the drainage of macromolecules from the CNS to the deep cervical lymph nodes. Importantly, the structural remodeling and maturation of meningeal lymphatics is impaired in γ mice with reduced lymph flow. Furthermore, macromolecule uptake and transport by the meningeal lymphatics are also affected in γ mice. Collectively, lymph flow-induced mechanical forces are required for the postnatal formation of mature and functional meningeal lymphatic vessels. Defining lymph flow-dependence of the development and function of meningeal lymphatics may lead to better understanding of the pathogenesis of neurological diseases including Alzheimer's disease and multiple sclerosis.
最近，在硬脑膜中已经证实并描述了淋巴管的存在，这与中枢神经系统（CNS）缺乏经典的淋巴引流系统的公认观点形成了对比。此外，脑膜淋巴管在阿尔茨海默病和多发性硬化症的发病机制中的作用也被提出。然而，脑膜淋巴管发育程序和功能的可能调节因子仍不清楚。在这里，我们旨在描述脑膜淋巴管发育程序和功能对淋巴流动的依赖性。首先，我们证明硬脑膜中的淋巴管参与了大分子从 CNS 的摄取和转运。脑膜淋巴管在出生后期间发育，这一过程涉及到血管的成熟。成熟脑膜淋巴管的形成与大分子从 CNS 向深部颈淋巴结的引流增加相吻合。重要的是，在淋巴流量减少的γ小鼠中，脑膜淋巴管的结构重塑和成熟受损。此外，脑膜淋巴管的大分子摄取和转运也受到γ小鼠的影响。总之，淋巴流动诱导的机械力是成熟和功能性脑膜淋巴管出生后形成所必需的。明确脑膜淋巴管发育和功能的淋巴依赖性可能有助于更好地理解包括阿尔茨海默病和多发性硬化症在内的神经疾病的发病机制。
