Tolerogenic Dendritic Cells as a Promising Antigen-Specific Therapy in the Treatment of Multiple Sclerosis and Neuromyelitis Optica From Preclinical to Clinical Trials.
Tolerogenic Dendritic Cells as a Promising Antigen-Specific Therapy in the Treatment of Multiple Sclerosis and Neuromyelitis Optica From Preclinical to Clinical Trials.
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DOI：
10.3389/fimmu.2018.01169
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发表时间：
2018
影响因子：
7.3
通讯作者：
Benitez-Ribas D
中科院分区：
文献类型：
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作者：
Flórez-Grau G;Zubizarreta I;Cabezón R;Villoslada P;Benitez-Ribas D
多发性硬化症 (MS) 患者血液中仅限于髓磷脂衍生免疫原性肽的活化 T 淋巴细胞和患者血液中视神经脊髓炎 (NMO) 中水通道蛋白 4 水通道的鉴定，为开发高选择性和疾病特异性治疗方法提供了可能性。抗原呈递细胞，特别是树突状细胞 (DC) 代表了抑制促炎 T 辅助细胞的策略。 DC 位于外周组织和淋巴组织中，对于 T 细胞依赖性免疫反应的稳态至关重要。参与病原体识别的一组特定受体的表达赋予树突状细胞启动免疫反应的特性。然而，在没有危险信号的情况下，不同的 DC 亚群已被证明可以通过诱导调节性 T 细胞、抑制促炎性 T 辅助细胞反应或两者来诱导主动耐受。有趣的是，已经描述了几种体外产生临床级耐受性 DC (Tol-DC) 的方案，为恢复中枢神经系统相关抗原的稳态提供了可能性。在这篇综述中，我们讨论了不同的 DC 子集及其在耐受诱导中的作用、生成 Tol-DC 的不同方案和动物模型中的临床前研究，并描述了 Tol-DC 在自身免疫性疾病（特别是 MS 和 NMO 患者）临床应用中的最新表征。此外，我们还讨论了正在进行的基于 Tol-DC 治疗不同自身免疫性疾病的临床试验。
The identification of activated T-lymphocytes restricted to myelin-derived immunogenic peptides in multiple sclerosis (MS) and aquaporin-4 water channel in neuromyelitis optica (NMO) in the blood of patients opened the possibility for developing highly selective and disease-specific therapeutic approaches. Antigen presenting cells and in particular dendritic cells (DCs) represent a strategy to inhibit pro-inflammatory T helper cells. DCs are located in peripheral and lymphoid tissues and are essential for homeostasis of T cell-dependent immune responses. The expression of a particular set of receptors involved in pathogen recognition confers to DCs the property to initiate immune responses. However, in the absence of danger signals different DC subsets have been revealed to induce active tolerance by inducing regulatory T cells, inhibiting pro-inflammatory T helper cells responses or both. Interestingly, several protocols to generate clinical-grade tolerogenic DC (Tol-DC) in vitro have been described, offering the possibility to restore the homeostasis to central nervous system-related antigens. In this review, we discuss about different DC subsets and their role in tolerance induction, the different protocols to generate Tol-DCs and preclinical studies in animal models as well as describe recent characterization of Tol-DCs for clinical application in autoimmune diseases and in particular in MS and NMO patients. In addition, we discuss the clinical trials ongoing based on Tol-DCs to treat different autoimmune diseases.