Anatomy and function of the vertebral column lymphatic network in mice

Laurent Jacob, Ligia Simoes Braga Boisserand, Luiz Henrique Medeiros Geraldo, Jose de Brito Neto, Thomas Mathivet, Salli Antila, Besma Barka, Yunling Xu, Jean-Mickael Thomas, Juliette Pestel, Marie-Stéphane Aigrot, Eric Song, Harri Nurmi, Seyoung Lee, Kari Alitalo, Nicolas Renier, Anne Eichmann & Jean-Leon Thomas

Nature Communications 10; 4594 (9 October 2019).

ABSTRACT:
Cranial lymphatic vessels (LVs) are involved in the transport of fluids, macromolecules and central nervous system (CNS) immune responses. Little information about spinal LVs is available, because these delicate structures are embedded within vertebral tissues and difficult to visualize using traditional histology. Here we show an extended vertebral column LV network using three-dimensional imaging of decalcified iDISCO+-clarified spine segments. Vertebral LVs connect to peripheral sensory and sympathetic ganglia and form metameric vertebral circuits connecting to lymph nodes and the thoracic duct. They drain the epidural space and the dura mater around the spinal cord and associate with leukocytes. Vertebral LVs remodel extensively after spinal cord injury and VEGF-C-induced vertebral lymphangiogenesis exacerbates the inflammatory responses, T cell infiltration and demyelination following focal spinal cord lesion. Therefore, vertebral LVs add to skull meningeal LVs as gatekeepers of CNS immunity and may be potential targets to improve the maintenance and repair of spinal tissues.