Anti-CD11b antibody treatment suppresses the disease conditions in rheumatoid arthritis (RA)-prone, FcγRIIB-deficient mice

Abstract

Abstract Previously we established a RA-prone, FcγRIIB deficient mouse strain (KO1). Anti-mouse CD11b mAb (5C6) has been reported to inhibit the recruitment of CD11b+ myelomonocytic cells from the blood to the inflammatory site. The CD11b+ cells include neutrophils and monocytes, both of which are known to play important roles in the development of RA. In this study, we treated KO1 mice with 5C6 mAb to examine its effects on RA development. Four-month-old preclinical KO1 mice were treated for 6 months; with 5C6, rat IgG as a control, or none. Among the 3 groups of mice, the severity of RA and immunological abnormalities were compared. RA-related factors in the ankle joints, spleens, and peripheral blood cells were examined. The 5C6 treatment ameliorated the conditions of RA in KO1 mice, along with the decreases in inflammatory-cell infiltration and osteoclast formation. Transcriptional level analysis for the ankle joints showed that the 5C6 treatment down-regulated the expressions of RANK, RANKL, MCP-1, RANTES, TNFα, and IL-6; and up-regulated that of osteoprotegerin, the decoy receptor for RANKL. Suppression of RA was associated with the lower serum level of autoantibodies, and the decreased frequency of activated B cells. Expressions of B-cell stimulating cytokines were suppressed in the spleens and peripheral leukocytes of the 5C6-treated mice. While untreated KO1 mice spontaneously developed marked monocytosis, the frequency of monocytes was significantly downregulated in the 5C6-treated mice. It is thought that the 5C6-mediated suppression of RA is caused by the decreased numbers of inflammatory cells and monocytes per se at the joints; also secondarily by the reduced amounts of B-cell stimulating cytokines, leading less autoantibodies.