Expression of MDC/CCL22 and its receptor CCR4 in rheumatoid arthritis, psoriatic arthritis and osteoarthritis.
The pathogenesis of rheumatoid arthritis (RA) and psoriatic arthritis (PsA) involves an abnormal chemokine regulation. The chemokine receptor CCR4 is necessary for T cell migration to the skin. We, therefore, studied if CCR4 and its ligand macrophage-derived chemokine (MDC/CCL22) could participate in spreading the disease between skin and joints by examining RA, PsA and osteoarthritis (OA) patients. In synovial fluid from RA and PsA patients we observed a significantly higher MDC/CCL22 level compared to OA patients. Additionally, the MDC/CCL22 protein was found to be elevated in RA and PsA plasma compared to OA and healthy volunteers. Flow cytometry revealed that most CD4(+)CCR4(+) lymphocytes also co-expressed CD45RO. Neither the MDC/CCL22 level nor the expression of CCR4 correlated to CRP. Immunohistochemistry of the RA and OA synovial membrane demonstrated CCR4 to be expressed by mononuclear cells and endothelial cells. Our results show that MDC/CCL22 is present within the synovial membrane of RA and OA patients and in high amount in the synovial fluid of patients with RA and PsA. This will enable migration of CCR4 expressing memory cells supporting that MDC/CCR4 could play a role in attracting skin specific memory T cells to the joints.
Flytlie
Helene Aarslev
HA
Institute of Medical Microbiology and Immunology, Aarhus University, DK-8000 Aarhus C, Denmark. helene.aarslev@immunology.au.dk
Hvid
Malene
M
Lindgreen
Esther
E
Kofod-Olsen
Emil
E
Petersen
Eva Lykke
EL
Jørgensen
Anette
A
Deleuran
Mette
M
Vestergaard
Christian
C
Deleuran
Bent
B
D000368:Aged; D000818:Animals; D015535:Arthritis, Psoriatic / Q000276:immunology* / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000473:pathology; D054422:Chemokine CCL22 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology; D008875:Middle Aged; D010003:Osteoarthritis / Q000276:immunology* / Q000473:pathology; D054398:Receptors, CCR4 / Q000235:genetics / Q000378:metabolism*; D012867:Skin / Q000276:immunology; D013582:Synovial Fluid / Q000276:immunology; D013583:Synovial Membrane / Q000166:cytology / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
C515482:CCL22 protein, human; D054422:Chemokine CCL22; D054398:Receptors, CCR4