Characterization of pericytes during autoreactive immune cell invasion into the CNS

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15m
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The blood-brain barrier (BBB) is a major regulator of the central nervous system (CNS) homeostasis. In numerous neurological disorders the impairment of the BBB leads to the entry of immune cells and molecules into the CNS causes neuronal dysfunction and degeneration. Although there is a growing interest in understanding the role of pericytes as component of the BBB, little is known about their impact in CNS autoimmunity. In this project we aim to elucidate the involvement of pericytes in maintenance of the BBB and modulation of immune cell invasion during CNS inflammation. To address this, we performed in vitro and in vivo experiments with an inducible pericyte-specific Cre mouse strain. As in vivo model for (CNS) inflammation we performed LPS injections and experimental autoimmune encephalitis (EAE) experiments. Flow cytometric analysis of in vivo experiments exhibited a modulation of adhesion and antigen-presenting molecules upon inflammation. In vitro assays revealed a capacity of brain pericytes to present antigens towards T cells and promote T cell adhesion. Reciprocally, an influence of immune cells on pericyte morphology and activity could be demonstrated. In conclusion, we propose that brain pericytes may modulate CNS inflammation by direct interaction with invading T cells.

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