Development of the antibody medical treatment to autoimmune and asthmatic diseases based on new target molecule.

在这项研究中，我们证明了TIM-4对胶原诱导的关节炎（CIA）和胶原抗体诱导的关节炎（CAIA）的发展的关键贡献，这是人类类风湿性关节炎的成熟动物模型。抗TIM-4 mAb的给药显著抑制了CIA和CAIA的发展，同时踝关节中的IL-6和IL-1 β降低。重要的是，与幼稚小鼠相比，在CIA小鼠的血清中检测到高水平的可溶性TIM-4。此外，可溶性TIM-4刺激显著诱导巨噬细胞产生IL-6和TNF-α。这些作用可能通过TIM-4-LMIR 5相互作用介导。值得注意的是，当在关节炎发作后或甚至在关节炎建立后施用抗TIM-4 mAb时，观察到抗TIM-4 mAb对关节炎的发展和进展的抑制作用。因此，TIM-4代表了类风湿性关节炎干预的新靶点。

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.