Characterization and recruitment of plasmacytoid dendritic cells in synovial fluid and tissue of patients with chronic inflammatory arthritis.
Dendritic cells (DCs) are thought to play a key role in driving the immunopathogenic response underlying chronic inflammatory arthritis. In this study, we have examined the presence and phenotype of plasmacytoid DCs (pDCs) in the synovial fluids (SF) of patients with rheumatoid arthritis (RA), psoriatic arthritis (PA), and osteoarthritis (OA) and determined the chemotactic properties of SF from these patients toward pDCs. Flow cytometry analysis showed that the percentage of pDCs, identified as a population of Lin(-)CD123(++) cells, is 4- to 5-fold higher in RA SF and PA SF than in OA SF. The morphological and immunophenotypic characterization of pDCs isolated from PA and RA SF indicates that they are in an immature state, most likely due to inhibitory factors present in RA SF, but are still able to undergo maturation when exposed ex vivo to viral agent or unmethylated DNA. CD123(+) and BDCA2(+) pDCs were detected by immunohistochemistry in RA synovial tissue in which expression of the IFN-alpha-inducible protein MxA was also found, suggesting production of type I IFN by maturing pDCs. We also show that CXCR3 and CXCR4 are expressed by both blood-derived pDCs and pDCs isolated from RA and PA SF and that CXCL-10, CXCL-11, and CXCL-12 present in RA and PA SF stimulate chemotaxis of blood-derived pDCs. Altogether, these findings suggest that chemokine-driven recruitment of pDCs from the blood to the inflamed synovium could be important in the regulation of the immune response in chronic inflammatory arthritis.
Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanità, Rome, Italy.
Roberto
R
Lande
Elena
E
Giacomini
Barbara
B
Serafini
Barbara
B
Rosicarelli
Gian Domenico
GD
Sebastiani
Giovanni
G
Minisola
Umberto
U
Tarantino
Valeria
V
Riccieri
Guido
G
Valesini
Eliana M
EM
Coccia
D000954:Antigens, Surface / Q000276:immunology; D001168:Arthritis / Q000276:immunology* / Q000503:physiopathology; D002454:Cell Differentiation / Q000276:immunology; D054357:Chemokine CXCL10; D054371:Chemokine CXCL11; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D002908:Chronic Disease; D003713:Dendritic Cells / Q000166:cytology* / Q000502:physiology; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D007370:Interferon Type I / Q000096:biosynthesis; D053650:Interleukin-3 Receptor alpha Subunit; D010641:Phenotype; D054367:Receptors, CXCR3; D019718:Receptors, CXCR4 / Q000096:biosynthesis; D019707:Receptors, Chemokine / Q000096:biosynthesis; D016185:Receptors, Interleukin-3 / Q000378:metabolism; D013582:Synovial Fluid / Q000166:cytology* / Q000276:immunology; D013583:Synovial Membrane / Q000166:cytology* / Q000276:immunology
D000954:Antigens, Surface; C515202:CXCL11 protein, human; C515255:CXCL12 protein, human; C515187:CXCR3 protein, human; D054357:Chemokine CXCL10; D054371:Chemokine CXCL11; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; C115022:IL3RA protein, human; D007370:Interferon Type I; D053650:Interleukin-3 Receptor alpha Subunit; D054367:Receptors, CXCR3; D019718:Receptors, CXCR4; D019707:Receptors, Chemokine; D016185:Receptors, Interleukin-3