Stromal Cell-Derived Factor-1-CXC Chemokine Receptor 4 Interactions Play a Central Role in CD4+ T Cell Accumulation in Rheumatoid Arthritis Synovium

• Published in: The Journal of immunology (1950) 2000-12, Vol.165 (11), p.6590-6598
• Main Authors: Nanki, Toshihiro, Hayashida, Kenji, El-Gabalawy, Hani S, Suson, Sharon, Shi, Kenrin, Girschick, Hermann J, Yavuz, Sule, Lipsky, Peter E
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic - physiology; Antibodies, Monoclonal - pharmacology; Apoptosis - immunology; Arthritis, Rheumatoid - blood; Arthritis, Rheumatoid - immunology; Arthritis, Rheumatoid - pathology; CD4 Antigens - biosynthesis; CD4 Antigens - blood; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD4-Positive T-Lymphocytes - pathology; CD40 Antigens - immunology; Cell Communication - immunology; Cell Membrane - immunology; Cell Membrane - metabolism; Cell Movement - immunology; Chemokine CXCL12; Chemokines, CXC - metabolism; Chemokines, CXC - physiology; Fibroblasts - immunology; Fibroblasts - metabolism; Fibroblasts - pathology; Humans; Interleukin-15 - pharmacology; Leukocyte Common Antigens - biosynthesis; Leukocyte Common Antigens - blood; Lymphocyte Activation - immunology; Osteoarthritis - immunology; Osteoarthritis - metabolism; Osteoarthritis - pathology; Receptors, CXCR4 - biosynthesis; Receptors, CXCR4 - genetics; Receptors, CXCR4 - metabolism; Receptors, CXCR4 - physiology; RNA, Messenger - biosynthesis; Stromal Cells - immunology; Synovial Membrane - immunology; Synovial Membrane - metabolism; Synovial Membrane - pathology; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - pathology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.165.11.6590

Rheumatoid arthritis (RA) is characterized by the accumulation of CD4(+) memory T cells in the inflamed synovium. To address the mechanism, we analyzed chemokine receptor expression and found that the frequency of CXC chemokine receptor (CXCR)4 expressing synovial tissue CD4(+) memory T cells was significantly elevated. CXCR4 expression could be enhanced by IL-15, whereas stromal cell-derived factor (SDF)-1, the ligand of CXCR4, was expressed in the RA synovium and could be increased by CD40 stimulation. SDF-1 stimulated migration of rheumatoid synovial T cells and also inhibited activation-induced apoptosis of T cells. These results indicate that SDF-1-CXCR4 interactions play important roles in CD4(+) memory T cell accumulation in the RA synovium, and emphasize the role of stromal cells in regulating rheumatoid inflammation.