Revisiting the CNS immune privilege

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Immune cells and their derived molecules have major impact on brain function. Mice deficient in adaptive immunity have impaired cognitive and social function compared to that of wild-type mice. Importantly, replenishment of the T cell compartment in immune deficient mice restored proper brain function. We have identified several key T cell-derived cytokines that mediate the effect. Despite the robust influence on brain function, T cells are not found within the brain parenchyma, a fact that only adds more mystery into these enigmatic interactions between T cells and the brain. Our results suggest that meningeal space, surrounding the brain, is the site where CNS-associated immune activity takes place. We have recently discovered a presence of meningeal lymphatic vessels that drain CNS molecules and immune cells to the deep cervical lymph nodes and also regulate perfusion of the brain by CSF (glymphatic flow). This communication between the CNS and meninges is playing a key role in several neurological and psychiatric disorders and, therefore, may serve as a novel therapeutic target that is worth in-depth mechanistic exploration. Understanding trafficking of molecules between CNS compartment is one of the frontiers in neurophysiology and recent advanced will be discussed.