Stromal cell-derived factor-1-CXC chemokine receptor 4 interactions play a central role in CD4+ T cell accumulation in rheumatoid arthritis synovium.
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.
Nanki
T
T
Department of Internal Medicine and Harold C. Simmons Arthritis Research Center, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75235, USA.
Hayashida
K
K
El-Gabalawy
H S
HS
Suson
S
S
Shi
K
K
Girschick
H J
HJ
Yavuz
S
S
Lipsky
P E
PE
D000276:Adjuvants, Immunologic / Q000502:physiology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000276:immunology* / Q000473:pathology; D015704:CD4 Antigens / Q000096:biosynthesis / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D019013:CD40 Antigens / Q000276:immunology; D002450:Cell Communication / Q000276:immunology; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D002465:Cell Movement / Q000276:immunology*; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000378:metabolism / Q000502:physiology*; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D019409:Interleukin-15 / Q000494:pharmacology; D017493:Leukocyte Common Antigens / Q000096:biosynthesis / Q000097:blood; D008213:Lymphocyte Activation / Q000276:immunology; D010003:Osteoarthritis / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis; D019718:Receptors, CXCR4 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D017154:Stromal Cells / Q000276:immunology; D013583:Synovial Membrane / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000473:pathology
D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D019013:CD40 Antigens; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D019409:Interleukin-15; D012333:RNA, Messenger; D019718:Receptors, CXCR4; D017493:Leukocyte Common Antigens