Cited by 686Barrier Structure and Function StudiesMultiple Sclerosis Research StudiesCell Adhesion Molecules Research

Capture, crawl, cross: the T cell code to breach the blood–brain barriers

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Engelhardt, Britta, Ransohoff, Richard M.·2012·Trends in Immunology

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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Crossref · 10.1016/j.it.2012.07.004

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88 of 88 references verified0 citation errors · 0 not checkable

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  • In experimental autoimmune encephalomyelitis models, a key pathophysiological event is encephalitogenic leukocyte CNS infiltration across the blood-brain barrier via sequential steps of capture, rolling, activation, adhesion, crawling, and diapedesis in postcapillary venules, capillaries, and mid-capillaries.

    “Experimental findings in MS models of chronic and relapsing EAE have shown that a key pathophysiological event is encephalitogenic leukocyte CNSinfiltration across the BBB that occurs via sequential steps of capture, rolling, activation, adhesion, crawling, and diapedesis in postcapillary venules, capillaries, and mid-capillaries (161, 182, 215, 216, 456, 617)”

    From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [161]

  • Paracellular diapedesis is regulated by endothelial VE-cadherin, JAM-A, ESAM, PECAM1, and CD99 and leukocyte LFA-1, PECAM1, and CD99.

    “Paracellular diapedesis is regulated by endothelial VE-cadherin, JAM-A, ESAM, PECAM1, and CD99 and leukocyte LFA-1, PECAM1, and CD99 (161, 215, 617) (FIGURE 10) .”

    From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [161]

  • Leukocyte migration across the BBB is limited to very few activated CD8+ and CD4+ T cells but not innate immune cells.

    “In fact, leukocyte migration across the BBB is limited to very few activated CD8+ and CD4+ T cells but not innate immune cells (80).”

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Authors
Engelhardt, B., & Ransohoff, R. M.
Affiliations
  • University of Bern (CH)
  • Cleveland Clinic (US)
Corresponding author
Engelhardt, Britta
Venue
Trends in Immunology
Publisher
Elsevier BV
Published
2012-12
Volume
33
Issue
12
Pages
579-589
ISSN
1471-4906 (ISSN-L)
OpenAlex
W2045683532
Cited by
686
References
88
Citations by year
2026: 43 · 2025: 49 · 2024: 50 · 2023: 45 · 2022: 56 · 2021: 49 · 2020: 56 · 2019: 42 · 2018: 59 · 2017: 45 · 2016: 52 · 2015: 55 · 2014: 42 · 2013: 42 · 2012: 1
FWCI
4.17
Type
journal article
Language
en
Open access
Locations
  • Trends in Immunology (publishedVersion)
  • PubMed (publishedVersion)
  • BORIS (University Library Bern) (submittedVersion)
  • Zenodo (CERN European Organization for Nuclear Research) (submittedVersion, other-oa)
Funders
  • National Institutes of Health
  • National Institute of Neurological Disorders and Stroke (K24 NS51400, P50NS38667, R21NS78420, R01NS32151, R01NS032151, K24NS051400, P50NS038667)
  • Rocky Mountain Research Station
Topics
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
  • Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
Keywords
blood-brain barrier, blood-CSF barrier, choroid plexus, T cell migration, glia limitans, multiple sclerosis, animal models of multiple sclerosis, cerebrospinal fluid
MeSH terms
Animals, Basement Membrane, Blood-Brain Barrier, Cell Movement, Central Nervous System, Humans, T-Lymphocytes

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