|Budget Amount *help
¥19,240,000 (Direct Cost: ¥14,800,000、Indirect Cost: ¥4,440,000)
Fiscal Year 2013: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2012: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2011: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
In this study, we demonstrated a critical contribution of TIM-4 to the development of collagen-induced arthritis (CIA) and collagen antibody-induced arthritis (CAIA), which are well-established animal model for the human rheumatoid arthritis. Administration of anti-TIM-4 mAb significantly inhibited the development of CIA and CAIA with a concomitant decrease of IL-6 and IL-1 beta in the ankle joints. Importantly, high levels of soluble TIM-4 were detected in sera of CIA mice as compared with naive mice. Moreover, soluble TIM-4 stimulation significantly induced IL-6 and TNF-alpha production by macrophages. These effects might be mediated by TIM-4-LMIR5 interaction. It is noteworthy that the inhibitory effects against the development and progression of arthritis by anti-TIM-4 mAb were observed when anti-TIM-4 mAb was administrated after the onset or even after the establishment of arthritis. TIM-4 thus represents a novel target for intervention of rheumatoid arthritis.