ArticleThe Journal of experimental medicine2014
VLA-4 blockade promotes differential routes into human CNS involving PSGL-1 rolling of T cells and MCAM-adhesion of TH17 cells.
Article in The Journal of experimental medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers.
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Who cites it
86 citing papers in PubMed, 143 citations in OpenAlex.
- Targeting CD4⁺ T cell infiltration: mechanisms and therapeutic insights into CD4⁺ T cell transmigration across the blood-brain barrier in acute ischemic stroke.Fluids and barriers of the CNS · 2026Review
- α4 Integrin blockade impairs CD8+ T cell neuroimmune surveillance following SIV infection.The Journal of clinical investigation · 2026Article
- Annual 12-Week Dosing Gap of Natalizumab: Clinical Efficacy, Blood Biomarkers, and CSF Cell Composition.Annals of clinical and translational neurology · 2026Observational
- Beta adrenergic signaling as a therapeutic target for autoimmunity.Journal of neuroimmunology · 2025Article
- Th17 cell pathogenicity in autoimmune disease.Experimental & molecular medicine · 2025Review
- In vitro morphological profiling of T cells predicts clinical response to natalizumab therapy in patients with multiple sclerosis.Nature communications · 2025Article
- Beta Adrenergic Signaling as a Therapeutic Target for Autoimmunity.bioRxiv : the preprint server for biology · 2025Article
- CD4+ T cell-innate immune crosstalk is critical during Staphylococcus aureus craniotomy infection.JCI insight · 2025Article
- Oligodendrocyte and Myelin Pathophysiology in Multiple Sclerosis.Advances in neurobiology · 2025Review
- CD146, a therapeutic target involved in cell plasticity.Science China. Life sciences · 2024Review
- Chemokine-mediated cell migration into the central nervous system in progressive multifocal leukoencephalopathy.Cell reports. Medicine · 2024Article
- A20 regulates lymphocyte adhesion in murine neuroinflammation by restricting endothelial ICOSL expression in the CNS.The Journal of clinical investigation · 2023Article
- Natalizumab Treatment Induces Proinflammatory CD4 T Cells Preferentially in the Integrin β7+ Compartment.Neurology(R) neuroimmunology & neuroinflammation · 2023Article
- Integrin α3 promotes TScience immunology · 2023Article
- Natalizumab Promotes Activation of Peripheral Monocytes in Patients With Multiple Sclerosis.Neurology(R) neuroimmunology & neuroinflammation · 2023Article
- Emerging Targets for Modulation of Immune Response and Inflammation in Stroke.Neurochemical research · 2023Review
- Effect of Previous Disease-Modifying Therapy on Treatment Effectiveness for Patients Treated With Ocrelizumab.Neurology(R) neuroimmunology & neuroinflammation · 2023Article
- Targeting MCAM for next-generation modulation of leucocyte trafficking.Brain : a journal of neurology · 2023Article
- MCAM+ brain endothelial cells contribute to neuroinflammation by recruiting pathogenic CD4+ T lymphocytes.Brain : a journal of neurology · 2023Article
- Learning multiple sclerosis immunopathogenesis from anti-CD20 therapy.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
26 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The focus of this study is the characterization of human T cell blood-brain barrier migration and corresponding molecular trafficking signatures. We examined peripheral blood and cerebrospinal fluid immune cells from patients under long-term anti-very late antigen-4 (VLA-4)/natalizumab therapy (LTNT) and from CNS specimens. LTNT patients' cerebrospinal fluid T cells exhibited healthy central-/effector-memory ratios, but lacked CD49d and showed enhanced myeloma cell adhesion molecule (MCAM) expression. LTNT led to an increase of PSGL-1 expression on peripheral T cells. Although vascular cell adhesion molecule-1 (VLA-4 receptor) was expressed at all CNS barriers, P-selectin (PSGL-1-receptor) was mainly detected at the choroid plexus. Accordingly, in vitro experiments under physiological flow conditions using primary human endothelial cells and LTNT patients' T cells showed increased PSGL-1-mediated rolling and residual adhesion, even under VLA-4 blockade. Adhesion of MCAM(+)/TH17 cells was not affected by VLA-4 blocking alone, but was abrogated when both VLA-4 and MCAM were inhibited. Consistent with these data, MCAM(+) cells were detected in white matter lesions, and in gray matter of multiple sclerosis patients. Our data indicate that lymphocyte trafficking into the CNS under VLA-4 blockade can occur by using the alternative adhesion molecules, PSGL-1 and MCAM, the latter representing an exclusive pathway for TH17 cells to migrate over the blood-brain barrier.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.