PDF(Pubmed)
Abstract：
Rheumatoid arthritis (RA) is a chronic inflammatory disease of the synovial joints that affects ~1% of the human population. Joint swelling and bone erosion, hallmarks of RA, contribute to disability and, sometimes, loss of life. Mechanistically, disease is driven by immune dysregulation characterized by circulating autoantibodies, inflammatory mediators, tissue degradative enzymes, and metabolic dysfunction of resident stromal and recruited immune cells. Cell death by apoptosis has been therapeutically explored in animal models of RA due to the comparisons drawn between synovial hyperplasia and paucity of apoptosis in RA with the malignant transformation of cancer cells. Several efforts to induce cell death have shown benefits in reducing the development and/or severity of the disease. Apoptotic cells are cleared by phagocytes in a process known as efferocytosis, which differs from microbial phagocytosis in its \"immuno-silent,\" or anti-inflammatory, nature. Failures in efferocytosis have been linked to autoimmune disease, whereas administration of apoptotic cells in RA models effectively inhibits inflammatory indices, likely though efferocytosis-mediated resolution-promoting mechanisms. However, the nature of signaling pathways elicited and the molecular identity of clearance mediators in RA are understudied. Furthermore, canonical efferocytosis machinery elements also play important non-canonical functions in homeostasis and pathology. Here, we discuss the roles of efferocytosis machinery components in models of RA and discuss their potential involvement in disease pathophysiology.
摘要：
类风湿性关节炎（RA）是滑膜关节的慢性炎性疾病，影响约1％的人口。关节肿胀和骨侵蚀，RA的标志，为残疾做出贡献，有时,失去生命。机械上,疾病是由以循环自身抗体为特征的免疫失调驱动的，炎症介质，组织降解酶，以及常驻基质和募集免疫细胞的代谢功能障碍。由于滑膜增生和RA中凋亡的缺乏与癌细胞的恶性转化之间的比较，已在RA的动物模型中对凋亡导致的细胞死亡进行了治疗性探索。诱导细胞死亡的若干努力已经显示出在降低疾病的发展和/或严重程度方面的益处。凋亡细胞被吞噬细胞清除，在一个被称为细胞凋亡的过程中，它与微生物吞噬的不同之处在于它的免疫沉默，\"或抗炎，性质。红细胞增多症的失败与自身免疫性疾病有关，而在RA模型中施用凋亡细胞可有效抑制炎症指标，可能是通过有效细胞增多介导的分辨率促进机制。然而,所引发的信号传导途径的性质和RA中清除介质的分子身份研究不足.此外，规范的Efferocytosis机械元件在稳态和病理学中也起着重要的非规范功能。这里,我们讨论了在RA模型中的作用，并讨论了它们在疾病病理生理学中的潜在参与。
