ArticleProceedings of the National Academy of Sciences of the United States of America2004
VLA-4 integrin concentrates at the peripheral supramolecular activation complex of the immune synapse and drives T helper 1 responses.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 144 citations in OpenAlex.
- Mechano-immunomodulatory biomaterials: From immune mechanosensing to translational design.Bioactive materials · 2026Review
- How crosstalk at the immune synapse shapes T cell and dendritic cell biology.Nature reviews. Immunology · 2026Review
- Single-cell profiling of tumor lineage plasticity and the immune microenvironment in transformed small cell lung cancer.Journal of translational medicine · 2026Article
- In vitro morphological profiling of T cells predicts clinical response to natalizumab therapy in patients with multiple sclerosis.Nature communications · 2025Article
- IL-7-mediated expansion of autologous lymphocytes increases CD8bioRxiv : the preprint server for biology · 2025Article
- Merocytophagy is an integrin-stabilized macrophage response to microbes reliant on Syk signaling.Frontiers in immunology · 2025Article
- Human T-cell receptor triggering requires inactivation of Lim kinase-1 by Slingshot-1 phosphatase.Communications biology · 2024Article
- Efficient gene deletion of Integrin alpha 4 in primary mouse CD4 T cells using CRISPR RNA pair-mediated fragmentation.Frontiers in immunology · 2024Article
- Analysis of humoral and cellular immunity after SARS-CoV-2 vaccination in patients with multiple sclerosis treated with immunomodulatory drugs.Clinical immunology communications · 2023Article
- Integrin α3 promotes TScience immunology · 2023Article
- Early posttransplant reductions in club cell secretory protein associate with future risk for chronic allograft dysfunction in lung recipients: results from a multicenter study.The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation · 2023Article
- Revisiting regulatory T cells as modulators of innate immune response and inflammatory diseases.Frontiers in immunology · 2023Review
- Impact of disease-modifying therapies on humoral and cellular immune-responses following SARS-CoV-2 vaccination in MS patients.Clinical and translational science · 2022Article
- LFA-1 and kindlin-3 enable the collaborative transport of SLP-76 microclusters by myosin and dynein motors.Journal of cell science · 2021Article
- Article
- Mucosal integrin α4β7 blockade fails to reduce the seeding and size of viral reservoirs in SIV-infected rhesus macaques.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Dysregulation of Leukocyte Trafficking in Type 2 Diabetes: Mechanisms and Potential Therapeutic Avenues.Frontiers in cell and developmental biology · 2021Review
- Tetraspanin CD53: an overlooked regulator of immune cell function.Medical microbiology and immunology · 2020Review
- Blockade of VLA4 sensitizes leukemic and myeloma tumor cells to CD3 redirection in the bone marrow microenvironment.Blood cancer journal · 2020Article
- Anti-αLβ2 antibodies reveal novel endocytotic cross-modulatory functionality.British journal of pharmacology · 2020Article
3 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The integrin alpha 4 beta 1 (VLA-4) not only mediates the adhesion and transendothelial migration of leukocytes, but also provides costimulatory signals that contribute to the activation of T lymphocytes. However, the behavior of alpha 4 beta 1 during the formation of the immune synapse is currently unknown. Here, we show that alpha 4 beta 1 is recruited to both human and murine antigen-dependent immune synapses, when the antigen-presenting cell is a B lymphocyte or a dendritic cell, colocalizing with LFA-1 at the peripheral supramolecular activation complex. However, when conjugates are formed in the presence of anti-alpha 4 antibodies, VLA-4 colocalizes with the CD3-zeta chain at the center of the synapse. In addition, antibody engagement of alpha 4 integrin promotes polarization toward a T helper 1 (Th1) response in human in vitro models of CD4(+) T cell differentiation and naïve T cell priming by dendritic cells. The in vivo administration of anti-alpha 4 integrin antibodies also induces an immune deviation to Th1 response that dampens a Th2-driven autoimmune nephritis in Brown Norway rats. These data reveal a regulatory role of alpha 4 integrins on T lymphocyte-antigen presenting cell cognate immune interactions.
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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.