The Hedgehog pathway promotes blood-brain barrier integrity and CNS immune quiescence |
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Authors: | Alvarez Jorge Ivan Dodelet-Devillers Aurore Kebir Hania Ifergan Igal Fabre Pierre J Terouz Simone Sabbagh Mike Wosik Karolina Bourbonnière Lyne Bernard Monique van Horssen Jack de Vries Helga E Charron Frédéric Prat Alexandre |
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Institution: | Neuroimmunology Unit, Center of Excellence in Neuromics, Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Faculty of Medicine, Université de Montréal, Montréal, Quebec, Canada. |
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Abstract: | The blood-brain barrier (BBB) is composed of tightly bound endothelial cells (ECs) and perivascular astrocytes that regulate central nervous system (CNS) homeostasis. We showed that astrocytes secrete Sonic hedgehog and that BBB ECs express Hedgehog (Hh) receptors, which together promote BBB formation and integrity during embryonic development and adulthood. Using pharmacological inhibition and genetic inactivation of the Hh signaling pathway in ECs, we also demonstrated a critical role of the Hh pathway in promoting the immune quiescence of BBB ECs by decreasing the expression of proinflammatory mediators and the adhesion and migration of leukocytes, in vivo and in vitro. Overall, the Hh pathway provides a barrier-promoting effect and an endogenous anti-inflammatory balance to CNS-directed immune attacks, as occurs in multiple sclerosis. |
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