Decreased IgG production but increased MIP-1beta expression in collagen-induced arthritis in C-C chemokine receptor 5-deficient mice.
Collagen-induced arthritis (CIA) is a widely used model of human rheumatoid arthritis (RA) characterized by chronic inflammation of the synovial joints. The pathogenesis of RA and CIA has not been completely defined, but both involve the recruitment of leukocytes and lymphocytes to the joints and Th1-type cell mediated autoimmune responses. The C-C chemokine receptor 5 (CCR5) is preferentially expressed on Th1 cells and has been strongly implicated in inflammatory process through trafficking of leukocytes and lymphocytes into the sites of inflammation. We investigated the role of the CCR5 in CIA using CCR5 knockout mice (CCR5-/-) in which we analyzed the consequences of CCR5 deficiency for the immune response and inflammation. We found that CCR5-/- mice showed a significant reduction in the incidence of CIA after collagen II (CII)-immunization as compared to wild-type (CCR5+/+) mice. The reduced incidence seen in CCR5-/- mice was associated with these animals having significantly lower IgG levels, especially IgG2a and IgG2b antibodies against CII, as well as an obviously augmented IL-10 production in splenocytes. Overproduction of MIP-1beta in CCR5-deficient mice after CII-immunization may contribute partially to the occurrence of arthritis.
Bao
Lei
L
Department of Orthopedic Surgery, Center for surgical sciences, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden. baoxx009@umn.edu
Zhu
Yu
Y
Zhu
Jie
J
Lindgren
J Urban
JU
D000818:Animals; D001169:Arthritis, Experimental / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D049109:Cell Proliferation; D002478:Cells, Cultured; D054407:Chemokine CCL4; D007074:Immunoglobulin G / Q000096:biosynthesis* / Q000276:immunology; D016753:Interleukin-10 / Q000378:metabolism; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D019713:Receptors, CCR5 / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism
D054407:Chemokine CCL4; D007074:Immunoglobulin G; D019402:Macrophage Inflammatory Proteins; D019713:Receptors, CCR5; D016753:Interleukin-10