Abstract
Abstract Recent studies show that meningeal lymphatic vessels surrounding the brain are quite reactive during neuroinflammatory disease states and can undergo changes in morphology to regulate the changing CNS microenvironment. It has been shown by our lab that cribriform plate lymphatic endothelial cells (cpLECs) functionally expand, proliferate, and change expressional profile in response to neuroinflammation. This shift in cpLEC phenotype is also associated with an increased affinity for leukocyte interactions, specifically dendritic cells (DCs). We hypothesize that these DC-cpLEC interactions are an important source of these lymphatic cell modifications and thus CNS homeostasis. However, the timing, origin, and full functional impact of peripheral DCs communication with cpLECs is unknown. In this study we attempted to track the arrival of peripherally stained DCs during neuroinflammation as they migrate to a cellular synapse with cpLECs. Utilizing a method of intravascular staining we found that peripherally stained DCs from the blood do not have immediate access to the cribriform lymphatics but can be observed bound to these lymphatic cells as early as 6hrs post injection, with steadily increases populations thereafter. Additionally, we mapped the migration of peripherally stained DCs across CNS parenchyma along key points of migration and infiltration like the choroid plexus, olfactory bulbs, and periventricular areas. Finally using novel methods of transgenic mice with photoconvertible cells, we validate that leukocytes bound to cpLECs have passed through the CNS parenchyma. Together these data attempt to characterize the complete circuit of migratory DCs pathway from the blood and through the CNS-lymphatic network.
Published Version
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