The Hedgehog pathway promotes blood-brain barrier integrity and CNS immune quiescence
- PMID: 22144466
- DOI: 10.1126/science.1206936
The Hedgehog pathway promotes blood-brain barrier integrity and CNS immune quiescence
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.
Comment in
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Neuroimmunology: a CNS guard as prickly as a hedgehog.Nat Rev Immunol. 2011 Dec 23;12(1):4. doi: 10.1038/nri3143. Nat Rev Immunol. 2011. PMID: 22193763 No abstract available.
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Neuroscience. Blood-brain barrier differentiation.Science. 2011 Dec 23;334(6063):1652-3. doi: 10.1126/science.1216853. Science. 2011. PMID: 22194564 No abstract available.
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