| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Outline of Final Research Achievements |
In this study, mice were treated with anti-TIM-4 mAb during the effector phase of collagen-induced arthritis (CIA). Treatment with anti-TIM-4 mAb just before or after the onset or even at later stage of CIA significantly suppressed the development and progression by reducing pro-inflammatory cytokines in the ankle joints without affecting T or B cell responses. Consistently, clinical arthritis scores of collagen antibody-induced arthritis (CAIA) were significantly reduced in anti-TIM-4-treated mice with a concomitant decrease of pro-inflammatory cytokines in the joints. In vitro, macrophages secreted pro-inflammatory cytokines in response to TIM-4-Ig protein and LPS, which were reduced by the anti-TIM-4 mAb. The anti-TIM-4 mAb also inhibited the differentiation and bone resorbing activity of osteoclasts. The therapeutic effect of anti-TIM-4 mAb is mediated by the inhibition of pro-inflammatory cytokine production by inflammatory cells, osteoclast differentiation, and bone resorption.
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