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Capture, crawl, cross: the T cell code to breach the blood-brain barriers
Britta Engelhardt1, Richard M Ransohoff
1Theodor Kocher Institute, University of Bern, Freiestrasse 1, CH-3012 Bern, Switzerland. bengel@tki.unibe.ch
Insights
Immune cells navigate the central nervous system (CNS) by crossing specialized barriers like the blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier (BCSFB). This review details the molecular mechanisms governing immune cell migration into the CNS, particularly in multiple sclerosis (MS).
Area of Science:
- Neuroimmunology
- Cellular Biology
- Pathophysiology
Background:
- The central nervous system (CNS) is protected by specialized barriers, including the blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier (BCSFB), which restrict immune cell entry.
- Immune cell infiltration into the CNS is a critical process in neuroinflammatory diseases like multiple sclerosis (MS).
Purpose of the Study:
- To review the molecular mechanisms controlling immune cell migration across the CNS barriers.
- To highlight the relevance of these mechanisms in the context of multiple sclerosis (MS) and its animal models.
Main Methods:
- This review synthesizes existing literature on immune cell trafficking across the BBB and BCSFB.
- Focus is placed on molecular interactions and cellular processes involved in barrier transmigration.
Main Results:
- Immune cell entry into the CNS involves a two-step process: crossing the BBB/BCSFB and then the glia limitans.
- Distinct molecular pathways regulate immune cell migration across the endothelial (BBB) and epithelial (BCSFB) barriers.
Conclusions:
- Understanding the specific molecular mechanisms of immune cell migration across CNS barriers is crucial for developing targeted therapies for MS.
- Differential regulation of immune cell trafficking provides potential therapeutic targets for modulating CNS inflammation.
Abstract:
The central nervous system (CNS) is an immunologically privileged site to which access of circulating immune cells is tightly controlled by the endothelial blood-brain barrier (BBB; see Glossary) localized in CNS microvessels, and the epithelial blood-cerebrospinal fluid barrier (BCSFB) within the choroid plexus. As a result of the specialized structure of the CNS barriers, immune cell entry into the CNS parenchyma involves two differently regulated steps: migration of immune cells across the BBB or BCSFB into the cerebrospinal fluid (CSF)-drained spaces of the CNS, followed by progression across the glia limitans into the CNS parenchyma. With a focus on multiple sclerosis (MS) and its animal models, this review summarizes the distinct molecular mechanisms required for immune cell migration across the different CNS barriers.
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