Division of Rheumatology, Universita' degli studi di Roma Tor Vergata, Rome, Italy.
Autoimmunity. 2010 Apr;43(3):220-5. doi: 10.3109/08916930903510914.
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disorder characterized by joint inflammation, immune cell infiltration of the synovia, and cartilage/bone destruction. Despite noteworthy progress in the treatment of RA in recent years, many patients remain refractory to current therapeutic strategies that target either the adaptive immune system or mediators of the innate system. Type I interferons (IFNs) play a significant role in regulation of the innate immune system, originally being discovered as part of intracellular immune defence against viral infection. IFNs are pleiotropic cytokines, mediating both immunostimulatory and immunosuppressive effects. IFN-alpha and beta have been detected in RA synovial fluid and tissue and subsequent therapeutic approaches using type I IFN in murine models of arthritis and in human RA have produced different and controversial results. Great interest has been directed toward principally plasmacytoid dendritic cells (pDCs), although also toward myeloid dendritic cells, as sources of type I IFN. Furthermore, manipulation of DC populations in murine RA models demonstrated that pDCs could suppress the development of arthritis and autoimmunity and may offer an attractive therapy for T-cell-mediated autoimmune diseases. Finally, dendritic cells (DCs) are vehicles for the delivery of therapeutic vaccines, and clinical trials are ongoing in RA with "tolerogenic" DC populations. Further, studies on animal models of RA will elucidate how IFN and DCs contribute to the establishment of autoimmune arthritis and the potential for manipulation of these cell populations and products to re-establish the immune tolerance.
类风湿关节炎（RA）是一种慢性炎症性自身免疫性疾病，其特征为关节炎症、免疫细胞浸润滑膜以及软骨/骨破坏。尽管近年来在 RA 的治疗方面取得了显著进展，但许多患者对目前针对适应性免疫系统或固有系统介质的治疗策略仍具有抗性。I 型干扰素（IFN）在固有免疫系统的调节中发挥着重要作用，最初被发现是作为细胞内抗病毒感染免疫防御的一部分。IFN 是多效细胞因子，介导免疫刺激和免疫抑制作用。在 RA 滑膜液和组织中检测到 IFN-α和 IFN-β，随后在关节炎的小鼠模型和人类 RA 中使用 I 型 IFN 的治疗方法产生了不同且有争议的结果。人们对主要来源于浆细胞样树突状细胞（pDC）的 IFN 产生了极大的兴趣，尽管对髓样树突状细胞作为 IFN 的来源也有兴趣。此外，在 RA 小鼠模型中对 DC 群体的操作表明，pDC 可以抑制关节炎和自身免疫的发展，并且可能为 T 细胞介导的自身免疫性疾病提供一种有吸引力的治疗方法。最后，树突状细胞（DC）是传递治疗性疫苗的载体，正在进行 RA 的“耐受性”DC 群体的临床试验。此外，对 RA 动物模型的研究将阐明 IFN 和 DC 如何有助于自身免疫性关节炎的建立，以及操纵这些细胞群体和产物以重新建立免疫耐受的潜力。
