San Raffaele Telethon Institute for Gene Therapy (OSR-TIGET), Division of Regenerative Medicine, Stem Cells and Gene Therapy, San Raffaele Scientific Institute, Milan, Italy.
Front Immunol. 2012 Aug 2;3:233. doi: 10.3389/fimmu.2012.00233. eCollection 2012.
Dendritic cells (DC) are antigen-presenting cells that play a pivotal role in regulating innate and adaptive immune responses. In autoimmunity, DC act as a double-edged sword since on one hand they initiate adaptive self-reactive responses and on the other they play a pivotal role in promoting and maintaining tolerance. Thus, DC are the most important cells in either triggering self-specific responses or in negatively regulating auto-reactive responses. The latter function is mediated by DC in the steady-state or specialized subsets of DC, named tolerogenic DC. Clinical and experimental evidence indicate that prolonged presentation of self-antigens by DC is crucial for the development of destructive autoimmune diseases, and defects in tolerogenic DC functions contribute to eradication of self-tolerance. In recent years, DC have emerged as therapeutic targets for limiting their immunogenicity against self-antigens, while tolerogenic DC have been conceived as therapeutic tools to restore tolerance. The purpose of this review is to give a general overview of the current knowledge on the pathogenic role of DC in patients affected by autoimmune diseases. In addition, the protective role of tolerogenic DC will be addressed. The currently applied strategies to block immune activation or to exploit the tolerogenic potential of DC will be discussed.
树突状细胞 (DC) 是一种抗原呈递细胞，在调节先天和适应性免疫反应中起着关键作用。在自身免疫中，DC 是一把双刃剑，因为一方面它们启动适应性自身反应，另一方面它们在促进和维持耐受中起着关键作用。因此，DC 是触发自身特异性反应或负调节自身反应的最重要的细胞。后一种功能是由 DC 在稳态或称为耐受性 DC 的专门亚群中介导的。临床和实验证据表明，DC 对自身抗原的长期呈递对于破坏性自身免疫疾病的发展至关重要，而耐受性 DC 功能的缺陷会导致自身耐受性的消除。近年来，DC 已成为限制其对自身抗原免疫原性的治疗靶点，而耐受性 DC 已被设想为恢复耐受的治疗工具。本综述的目的是概述目前关于 DC 在自身免疫性疾病患者中致病作用的知识。此外，还将讨论耐受性 DC 的保护作用。将讨论目前用于阻断免疫激活或利用 DC 耐受潜能的策略。
