Report

The Hedgehog Pathway Promotes Blood-Brain Barrier Integrity and CNS Immune Quiescence

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Science  01 Dec 2011:
1206936
DOI: 10.1126/science.1206936

Abstract

The blood-brain barrier (BBB) is composed of tightly bound endothelial cells (ECs) and perivascular astrocytes that regulate central nervous system (CNS) homeostasis. Here, we show that astrocytes secrete Sonic hedgehog (Shh) and that BBB-ECs express 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 demonstrate a critical role of the Hh pathway in promoting 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.