The hallmark of autoimmune arthritis is the preceding autoantibody production and the following synovial inflammation with hyperplasia and tissue destruction of the joints. The joint inflammation is mediated not only by effector lymphocytes and auto-antibodies but also chronic activation of innate immunity, particularly promoted by the danger-associated molecular patterns (DAMPs). Here we show that apoptosis inhibitor of macrophage (AIM, also called CD5L) protein regulates arthritis by promoting removal of lesional DAMPs both physiologically and therapeutically. When the autoimmune arthritis was promoted by injecting a cocktail of anti-collagen antibodies without type-II collagen immunization, AIM-deficient () mice exhibited more exacerbated and sustained swelling at multiple joints with greater synovial hyperplasia and bone erosion than wild-type mice. Administration of recombinant AIM (rAIM) reduced S100A8/9, a major DAMP known to be involved in arthritis progression, and decreased various inflammatory cytokines at the lesions in antibody-injected mice, leading to marked prevention of arthritis symptoms. In human rheumatoid arthritis (RA) patients, AIM was more activated via dissociating from IgM-pentamer in response to DAMPs-mediated inflammation both in serum and synovial fluid than in healthy individuals or non-autoimmune osteoarthritis patients, suggesting a disease-regulatory potency of AIM also in human RA patients. Thus, our study implied a therapeutic availability of rAIM to prevent arthritis symptoms targeting DAMPs.

中文翻译：

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AIM/CD5L 通过促进病灶处炎症 DAMP 的去除来改善自身免疫性关节炎

自身免疫性关节炎的特点是先产生自身抗体，然后出现滑膜炎症，伴有关节增生和组织破坏。关节炎症不仅由效应淋巴细胞和自身抗体介导，而且还由先天免疫的慢性激活介导，特别是由危险相关分子模式（DAMP）促进。在这里，我们发现巨噬细胞凋亡抑制剂（AIM，也称为 CD5L）蛋白通过促进病变 DAMP 的清除来调节关节炎的生理和治疗作用。当通过注射抗胶原抗体混合物而不进行II型胶原免疫来促进自身免疫性关节炎时，与野生型小鼠相比，AIM缺陷型小鼠在多个关节处表现出更严重和持续的肿胀，滑膜增生和骨质侵蚀更严重。重组 AIM (rAIM) 的施用可减少 S100A8/9（一种已知参与关节炎进展的主要 DAMP），并减少注射抗体的小鼠病变处的各种炎症细胞因子，从而显着预防关节炎症状。在人类类风湿性关节炎 (RA) 患者中，与健康个体或非自身免疫性骨关节炎患者相比，AIM 通过与 IgM 五聚体解离来响应血清和滑液中 DAMP 介导的炎症而更加激活，这表明 AIM 的疾病调节效力AIM 也适用于人类 RA 患者。因此，我们的研究表明 rAIM 具有针对 DAMP 来预防关节炎症状的治疗作用。