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

被引：615

作者：

Alvarez, Jorge Ivan ^{[1
]}

Dodelet-Devillers, Aurore ^{[1
]}

Kebir, Hania ^{[1
]}

Ifergan, Igal ^{[1
]}

Fabre, Pierre J. ^{[2
,3
]}

Terouz, Simone ^{[1
]}

Sabbagh, Mike ^{[1
]}

Wosik, Karolina ^{[1
]}

Bourbonniere, Lyne ^{[1
]}

Bernard, Monique ^{[1
]}

van Horssen, Jack ^{[4
]}

de Vries, Helga E. ^{[4
]}

Charron, Frederic ^{[2
,3
]}

Prat, Alexandre ^{[1
]}

机构：

[1] Univ Montreal, Ctr Rech, Ctr Excellence Neur, Neuroimmunol Unit,Ctr Hosp Univ Montreal,Fac Med, Montreal, PQ H2L 4M1, Canada

[2] Univ Montreal, Inst Rech Clin Montreal, Lab Mol Biol Neural Dev, Montreal, PQ H2W 1R7, Canada

[3] Univ Montreal, Dept Med, Montreal, PQ H2W 1R7, Canada

[4] Vrije Univ Amsterdam Med Ctr, Dept Mol Cell Biol & Immunol, NL-1007 MB Amsterdam, Netherlands

来源：

SCIENCE | 2011年 / 334卷 / 6063期

基金：

加拿大健康研究院;

关键词：

CENTRAL-NERVOUS-SYSTEM; ASTROCYTE-ENDOTHELIAL INTERACTIONS; MULTIPLE-SCLEROSIS; AUTOIMMUNE ENCEPHALOMYELITIS; SPECIFICATION; ANGIOGENESIS; INFLAMMATION; LYMPHOCYTES; DISRUPTION; EXPRESSION;

D O I：

10.1126/science.1206936

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：1727 / 1731

页数：5

共 35 条

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