title: Inhibition of fractalkine ameliorates murine collagen-induced arthritis.
abstract: Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with massive infiltration of inflammatory cells in the synovium of multiple joints. We and others have shown that fractalkine (FKN/CX3CL1), a chemokine expressed on fibroblast-like synoviocytes and endothelial cells in RA synovium, may contribute to the accumulation of T cells, macrophages, and dendritic cells, which express CX3CR1, the receptor for FKN. This interaction might be involved in adhesion of the inflammatory cells to endothelial cells, migration into the synovium, and cytokine production. In this study, we examined the effect of FKN inhibition on murine collagen-induced arthritis. Anti-FKN mAb significantly lowered clinical arthritis score compared with control Ab, and reduced infiltration of inflammatory cells and bone erosion in the synovium. However, anti-FKN mAb did not affect the production of either serum anti-collagen type II (CII) IgG or IFN-gamma by CII-stimulated splenic T cells. Furthermore, treatment with anti-FKN mAb inhibited migration of adoptively transferred splenic macrophages into the inflamed synovium. Our results suggest that anti-FKN mAb ameliorates arthritis by inhibiting infiltration of inflammatory cells into the synovium. Thus, FKN can be a new target molecule for the treatment of RA.
authors.affiliation: Department of Medicine and Rheumatology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan. nanki.rheu@tmd.ac.jp
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Nanki
authors.forename: Yasuyo
authors.initials: Y
authors.lastname: Urasaki
authors.forename: Toshio
authors.initials: T
authors.lastname: Imai
authors.forename: Miyuki
authors.initials: M
authors.lastname: Nishimura
authors.forename: Kenzo
authors.initials: K
authors.lastname: Muramoto
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Kubota
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Miyasaka
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000008:administration & dosage; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D001169:Arthritis, Experimental / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D000073883:CX3C Chemokine Receptor 1; D002417:Cattle; D002464:Cell Migration Inhibition; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D024043:Collagen Type II / Q000008:administration & dosage / Q000276:immunology*; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000097:blood; D007150:Immunohistochemistry; D007274:Injections, Intraperitoneal; D007371:Interferon-gamma / Q000096:biosynthesis; D008264:Macrophages / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D051379:Mice; D008811:Mice, Inbred DBA; D019707:Receptors, Chemokine / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D013583:Synovial Membrane / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D000073883:CX3C Chemokine Receptor 1; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C; D024043:Collagen Type II; C515539:Cx3cl1 protein, mouse; C471885:Cx3cr1 protein, mouse; D007074:Immunoglobulin G; D008565:Membrane Proteins; D019707:Receptors, Chemokine; D007371:Interferon-gamma