Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2000-10-10
pubmed:abstractText
Chemokines and their receptors determine the distribution of leukocytes within tissues in health and disease. We have studied the role of the constitutive chemokine receptor CXCR4 and its ligand, stromal-derived factor-1 (SDF-1) in the perivascular accumulation of T cells in rheumatoid arthritis. We show that synovial T cells, which are primed CD45RO+CD45RBdull cells and consequently not expected to express constitutive chemokine receptors, have high levels of the chemokine receptor CXCR4. Sustained expression of CXCR4 was maintained on synovial T cells by specific factors present within the synovial microenvironment. Extensive screening revealed that TGF-beta isoforms induce the expression of CXCR4 on CD4 T cells in vitro. Depletion studies using synovial fluid confirmed an important role for TGF-beta1 in the induction of CXCR4 expression in vivo. The only known ligand for CXCR4 is SDF-1. We found SDF-1 on synovial endothelial cells and showed that SDF-1 was able to induce strong integrin-mediated adhesion of synovial fluid T cells to fibronectin and ICAM-1, confirming that CXCR4 expressed on synovial T cells was functional. These results suggest that the persistent induction of CXCR4 on synovial T cells by TGF-beta1 leads to their active, SDF-1-mediated retention in a perivascular distribution within the rheumatoid synovium.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
165
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3423-9
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:10975862-Arthritis, Rheumatoid, pubmed-meshheading:10975862-CD4-Positive T-Lymphocytes, pubmed-meshheading:10975862-Cell Differentiation, pubmed-meshheading:10975862-Cell Line, pubmed-meshheading:10975862-Cell Movement, pubmed-meshheading:10975862-Cells, Cultured, pubmed-meshheading:10975862-Chemokine CXCL12, pubmed-meshheading:10975862-Chemokines, CXC, pubmed-meshheading:10975862-Endothelium, Vascular, pubmed-meshheading:10975862-Humans, pubmed-meshheading:10975862-Lymphocyte Activation, pubmed-meshheading:10975862-Receptors, CXCR4, pubmed-meshheading:10975862-Stromal Cells, pubmed-meshheading:10975862-Synovial Fluid, pubmed-meshheading:10975862-Synovial Membrane, pubmed-meshheading:10975862-T-Lymphocyte Subsets, pubmed-meshheading:10975862-Transforming Growth Factor beta
pubmed:year
2000
pubmed:articleTitle
Persistent induction of the chemokine receptor CXCR4 by TGF-beta 1 on synovial T cells contributes to their accumulation within the rheumatoid synovium.
pubmed:affiliation
Division of Immunity and Infection, Medical Research Council Center for Immune Regulation, University of Birmingham, Edgbaston, United Kingdom. c.d.buckley@bham.ac.uk
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't