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According to the current model for tissue-specific homing, specificity is conferred by the selective recruitment of lymphocyte populations from peripheral blood, based on their expression of chemokine and adhesion receptors (endothelial selection). In this study, we provide evidence for an alternative stromal induction mechanism that operates in chronic inflammation. We show that the human rheumatoid synovial microenvironment directly induces functional inflammatory (CCR5 and CXCR3) and constitutive (CCR7 and CXCR4) chemokine receptors on infiltrating CD4(+) T cells. Expression of the corresponding inflammatory chemokine ligands (CCL5 and CXCL11) was confined to stromal areas in the synovium. However, expression of the constitutive ligands (CCL19 and CXCL12) was inappropriately high on both vascular and lymphatic endothelium, suggesting that the vascular to lymphatic chemokine gradient involved in lymphatic recirculation becomes subverted in the rheumatoid synovium. These results challenge the view that leukocyte trafficking is regulated solely by selective recruitment of pre-existing chemokine receptor-positive cells from peripheral blood, by providing an alternative explanation based on aberrant lymphocyte retention and compromised lymphatic return.

Original publication

DOI

10.4049/jimmunol.174.3.1693

Type

Journal article

Journal

Journal of immunology (Baltimore, Md. : 1950)

Publication Date

02/2005

Volume

174

Pages

1693 - 1700

Addresses

Medical Research Council Centre for Immune Regulation, Institute of Biomedical Research, University of Birmingham, Birmingham, United Kingdom.

Keywords

Synovial Membrane, Synovial Fluid, Endothelium, Vascular, Endothelium, Lymphatic, Lymphocyte Subsets, CD4-Positive T-Lymphocytes, Cells, Cultured, Stromal Cells, Humans, Arthritis, Rheumatoid, Receptors, Chemokine, Receptors, CXCR4, Chemokines, CC, Chemokines, CXC, Cell Communication, Chemotaxis, Leukocyte, Immunologic Memory, Receptors, CXCR3, Chemokine CXCL12, Chemokine CCL19, Resting Phase, Cell Cycle