Khan Shaukat, Greenberg Jeffrey D, Bhardwaj Nina
Cancer Institute, New York University Langone Medical Center, and New York University Hospital for Joint Diseases, New York, NY 10016, USA.
Nat Rev Rheumatol. 2009 Oct;5(10):566-71. doi: 10.1038/nrrheum.2009.185.
Dendritic cells (DCs) are central in inducing immunity and in mediating immune tolerance in their role as professional antigen-presenting cells. In the absence of DCs, a fatal autoimmunity develops in animal models. Although the role of DCs has been investigated extensively in the pathogenesis of rheumatoid arthritis (RA), it remains unclear whether DCs initiate autoimmunity in this disease. Nevertheless, evidence points towards a significant role for DCs in disease maintenance and progression. Current biologic therapies target cytokine products of antigen-presenting cells, such as tumor necrosis factor, interleukin-1 and interleukin-6. Emerging therapies for RA exploit the tolerogenic capacity of DCs. 'Tolerogenic' DCs can be generated from myeloid precursors ex vivo, loaded with antigen, and manipulated to suppress autoimmune responses in vivo, through the induction of activation-induced cell death, anergy, and/or regulatory T cells. Cells that are primed by DCs, such as B cells, type 1 and type 17 T helper cells, and that have been implicated in certain models of autoimmunity, are also being considered as additional targets for immune-based therapy. Studies to validate these approaches to ameliorate autoimmunity will be necessary before their application in the clinic.
树突状细胞（DCs）作为专职抗原呈递细胞，在诱导免疫和介导免疫耐受方面发挥着核心作用。在缺乏DCs的情况下，动物模型中会发生致命的自身免疫。尽管DCs在类风湿关节炎（RA）发病机制中的作用已得到广泛研究，但DCs是否引发该疾病的自身免疫仍不清楚。然而，有证据表明DCs在疾病维持和进展中起重要作用。目前的生物疗法针对抗原呈递细胞的细胞因子产物，如肿瘤坏死因子、白细胞介素-1和白细胞介素-6。RA的新兴疗法利用了DCs的致耐受性。“致耐受性”DCs可在体外由髓样前体细胞产生，负载抗原，并通过诱导激活诱导的细胞死亡、无反应性和/或调节性T细胞，在体内进行操控以抑制自身免疫反应。由DCs致敏的细胞，如B细胞、1型和17型辅助性T细胞，在某些自身免疫模型中发挥作用，也被视为基于免疫疗法的额外靶点。在将这些改善自身免疫的方法应用于临床之前，有必要进行研究以验证其有效性。
