RGD Reference Report - VLA-4 integrin concentrates at the peripheral supramolecular activation complex of the immune synapse and drives T helper 1 responses. - Rat Genome Database

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VLA-4 integrin concentrates at the peripheral supramolecular activation complex of the immune synapse and drives T helper 1 responses.

Authors: Mittelbrunn, M  Molina, A  Escribese, MM  Yanez-Mo, M  Escudero, E  Ursa, A  Tejedor, R  Mampaso, F  Sanchez-Madrid, F 
Citation: Mittelbrunn M, etal., Proc Natl Acad Sci U S A. 2004 Jul 27;101(30):11058-63. Epub 2004 Jul 19.
RGD ID: 9698421
Pubmed: (View Article at PubMed) PMID:15263094
DOI: Full-text: DOI:10.1073/pnas.0307927101

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 naive 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.

Annotation

Gene Ontology Annotations    

Biological Process

Objects Annotated

Genes (Rattus norvegicus)
Itga4  (integrin subunit alpha 4)


Additional Information