Domogalla Matthias P, Rostan Patricia V, Raker Verena K, Steinbrink Kerstin
Department of Dermatology, Division for Experimental and Translational Research, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.
Research Center for Immunotherapy, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.
Front Immunol. 2017 Dec 11;8:1764. doi: 10.3389/fimmu.2017.01764. eCollection 2017.
Dendritic cells (DCs) are central players in the initiation and control of responses, regulating the balance between tolerance and immunity. Tolerogenic DCs are essential in the maintenance of central and peripheral tolerance by induction of clonal T cell deletion and T cell anergy, inhibition of memory and effector T cell responses, and generation and activation of regulatory T cells. Therefore, tolerogenic DCs are promising candidates for specific cellular therapy of allergic and autoimmune diseases and for treatment of transplant rejection. Studies performed in rodents have demonstrated the efficacy and feasibility of tolerogenic DCs for tolerance induction in various inflammatory diseases. In the last years, numerous protocols for the generation of human monocyte-derived tolerogenic DCs have been established and some first phase I trials have been conducted in patients suffering from autoimmune disorders, demonstrating the safety and efficiency of this cell-based immunotherapy. This review gives an overview about methods and protocols for the generation of human tolerogenic DCs and their mechanisms of tolerance induction with the focus on interleukin-10-modulated DCs. In addition, we will discuss the prerequisites for optimal clinical grade tolerogenic DC subsets and results of clinical trials with tolerogenic DCs in autoimmune diseases.
树突状细胞（DCs）是免疫应答启动和调控的核心参与者，调节着免疫耐受与免疫之间的平衡。致耐受性DCs通过诱导克隆性T细胞缺失和T细胞无能、抑制记忆性和效应性T细胞应答以及生成和激活调节性T细胞，在维持中枢和外周耐受中发挥着至关重要的作用。因此，致耐受性DCs是过敏性和自身免疫性疾病特异性细胞治疗以及移植排斥反应治疗的有前景的候选者。在啮齿动物中进行的研究已证明致耐受性DCs在各种炎症性疾病中诱导耐受的有效性和可行性。在过去几年中，已经建立了许多生成人单核细胞来源的致耐受性DCs的方案，并且已经在患有自身免疫性疾病的患者中进行了一些一期试验，证明了这种基于细胞的免疫疗法的安全性和有效性。本综述概述了生成人致耐受性DCs的方法和方案及其耐受诱导机制，重点是白细胞介素-10调节的DCs。此外，我们将讨论最佳临床级致耐受性DC亚群的先决条件以及自身免疫性疾病中致耐受性DCs的临床试验结果。
