ArticleProceedings of the National Academy of Sciences of the United States of America2009
Beta1 integrins differentially control extravasation of inflammatory cell subsets into the CNS during autoimmunity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
54 citing papers in PubMed, 104 citations in OpenAlex.
- Mast cells proliferate in the peri-hippocampal space during early development and modulate local and peripheral immune cells.Developmental cell · 2025Article
- Biphasic Hormetic-like Effect of Lebecetin, a C-type Lectin of Snake Venom, on Formalin-induced Inflammation in Mice.Current neuropharmacology · 2024Article
- Targeting Leukocyte Trafficking in Inflammatory Bowel Disease.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2021Article
- Pro-inflammatory T helper 17 directly harms oligodendrocytes in neuroinflammation.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Integrin-directed antibody-based immunotherapy: focus on VLA-4.Immunotherapy advances · 2021Review
- Immunological Bases of Paraneoplastic Cerebellar Degeneration and Therapeutic Implications.Frontiers in immunology · 2020Review
- Immune cell trafficking across the blood-brain barrier in the absence and presence of neuroinflammation.Vascular biology (Bristol, England) · 2020Review
- Imaging the dynamic interactions between immune cells and the neurovascular interface in the spinal cord.Experimental neurology · 2019Review
- Dendritic Cell Accumulation in the Gut and Central Nervous System Is Differentially Dependent on α4 Integrins.Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- Tissue Architectural Cues Drive Organ Targeting of Tumor Cells in Zebrafish.Cell systems · 2019Article
- Hectd3 promotes pathogenic Th17 lineage through Stat3 activation and Malt1 signaling in neuroinflammation.Nature communications · 2019Article
- Intercellular Adhesion Molecule-1 (ICAM-1) and ICAM-2 Differentially Contribute to Peripheral Activation and CNS Entry of Autoaggressive Th1 and Th17 Cells in Experimental Autoimmune Encephalomyelitis.Frontiers in immunology · 2019Article
- Post-Stroke Blood-Brain Barrier Disruption and Poor Functional Outcome in Patients Receiving Thrombolytic Therapy.Cerebrovascular diseases (Basel, Switzerland) · 2019Observational
- TLR3 agonism re-establishes CNS immune competence duringAnnals of clinical and translational neurology · 2018Article
- Integrins in T Cell Physiology.International journal of molecular sciences · 2018Review
- Serosal Cavities Contain Two Populations of Innate-like integrin α4Immune network · 2017Article
- T-bet-dependent NKp46Nature immunology · 2017Article
- Multiple sclerosis animal models: a clinical and histopathological perspective.Brain pathology (Zurich, Switzerland) · 2017Review
- Checkpoints to the Brain: Directing Myeloid Cell Migration to the Central Nervous System.International journal of molecular sciences · 2016Review
- VCAM1 acts in parallel with CD69 and is required for the initiation of oligodendrocyte myelination.Nature communications · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Inhibiting the alpha(4) subunit of the integrin heterodimers alpha(4)beta(1) and alpha(4)beta(7) with the monoclonal antibody natalizumab is an effective treatment for multiple sclerosis (MS). However, the pharmacological action of natalizumab is not understood conclusively. Previous studies suggested that natalizumab inhibits activation, proliferation, or extravasation of inflammatory cells. To specify which mechanisms, cell types, and alpha(4) heterodimers are affected by the antibody treatment, we studied MS-like experimental autoimmune encephalomyelitis (EAE) in mice lacking the beta(1)-integrin gene either in all hematopoietic cells or selectively in T lymphocytes. Our results show that T cells critically rely on beta(1) integrins to accumulate in the central nervous system (CNS) during EAE, whereas CNS infiltration of beta(1)-deficient myeloid cells remains unaffected, suggesting that T cells are the main target of anti-alpha(4)-antibody blockade. We demonstrate that beta(1)-integrin expression on encephalitogenic T cells is critical for EAE development, and we therefore exclude alpha(4)beta(7) as a target integrin of the antibody treatment. T cells lacking beta(1) integrin are unable to firmly adhere to CNS endothelium in vivo, whereas their priming and expansion remain unaffected. Collectively, these results suggest that the primary action of natalizumab is interference with T cell extravasation via inhibition of alpha(4)beta(1) integrins.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.