The hedgehog pathway promotes blood-brain barrier integrity and CNS immune quiescence

Jorge Ivan Alvarez, Aurore Dodelet-Devillers, Hania Kebir, Igal Ifergan, Pierre J. Fabre, Simone Terouz, Mike Sabbagh, Karolina Wosik, Lyne Bourbonnière, Monique Bernard, Jack Van Horssen, Helga E. De Vries, Frédéric Charron, Alexandre Prat*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

417 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1727-1731
Number of pages5
JournalScience
Volume334
Issue number6063
DOIs
StatePublished - Dec 23 2011

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'The hedgehog pathway promotes blood-brain barrier integrity and CNS immune quiescence'. Together they form a unique fingerprint.

Cite this