Suwandi Jessica S, Nikolic Tatjana, Roep Bart O
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, Netherlands.
Department of Diabetes Immunology, Diabetes & Metabolism Research Institute, Beckman Research Institute, City of Hope, Duarte, CA, United States.
Front Immunol. 2017 Nov 22;8:1598. doi: 10.3389/fimmu.2017.01598. eCollection 2017.
Tolerogenic dendritic cells (tolDCs) have reached patients with autoimmune and inflammatory disease, at least in clinical trials. The safety of tolDCs as intervention therapy has been established, but the capacity to modulate autoimmune response remains to be demonstrated. Studies have revealed a diversity of regulatory mechanisms that tolDCs may employ . These mechanisms differ between various types of modulated tolDC. The most often foreseen action of tolDCs is through regulatory polarization of naïve T cells or activation of existing regulatory T cells, which should ultimately diminish autoimmune inflammation. Yet, selection of a target autoantigen remains critical to expedite tissue specific tolerance induction, while measuring immune modulation incited by tolDCs provides a great challenge. We will discuss the regulatory action of different types of tolDCs and the possible methods to monitor immunological efficacy endpoints for the next generation clinical trials.
耐受性树突状细胞(tolDCs)至少在临床试验中已经应用于自身免疫性和炎性疾病患者。tolDCs作为干预疗法的安全性已经确立,但其调节自身免疫反应的能力仍有待证明。研究揭示了tolDCs可能采用的多种调节机制。这些机制在不同类型的经调节的tolDC之间存在差异。tolDCs最常被预见的作用是通过幼稚T细胞的调节性极化或现有调节性T细胞的激活,这最终应减轻自身免疫性炎症。然而,选择靶自身抗原对于加速组织特异性耐受性诱导仍然至关重要,而测量tolDCs引发的免疫调节则带来了巨大挑战。我们将讨论不同类型tolDCs的调节作用以及用于下一代临床试验监测免疫疗效终点的可能方法。