Dendritic cells treated with chloroquine modulate experimental autoimmune encephalomyelitis
Dendritic cells treated with chloroquine modulate experimental autoimmune encephalomyelitis
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DOI：
10.1038/icb.2013.73
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发表时间：
2014-02-01
影响因子：
4
通讯作者：
Verinaud, Liana
中科院分区：
文献类型：
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作者：
Thome, Rodolfo;Issayama, Luidy Kazuo;Verinaud, Liana
氯喹（CQ）是一种抗疟疾药物，已被证明可以调节免疫系统并降低实验性自身免疫性脑脊髓炎（EAE）的严重程度。疾病抑制的机制依赖于调节性T细胞诱导，尽管存在Tregs非依赖性机制。我们的目的是评估是否CQ是能够调节骨髓来源的树突状细胞（DC）的表型和功能，以及是否CQ调制的DC转移减少EAE过程。我们的研究结果表明，CQ处理的DC呈现改变的超微结构形态和参与抗原呈递的分子的表达降低。因此，在共培养实验中T细胞增殖减少。当转移到EAE小鼠中时，DC-CQ能够通过调节针对神经抗原的免疫应答来减少疾病的临床表现。本文提供的数据表明，氯喹介导的免疫系统调节是通过对DC的直接作用实现的，并且DC-CQ过继转移可能是避免药物毒性的有希望的方法。
Chloroquine (CQ), an antimalarial drug, has been shown to modulate the immune system and reduce the severity of experimental autoimmune encephalomyelitis (EAE). The mechanisms of disease suppression are dependent on regulatory T cell induction, although Tregs-independent mechanisms exist. We aimed to evaluate whether CQ is capable to modulate bone marrow-derived dendritic cells (DCs) both phenotypically and functionally as well as whether transfer of CQ-modulated DCs reduces EAE course. Our results show that CQ-treated DCs presented altered ultrastructure morphology and lower expression of molecules involved in antigen presentation. Consequently, T cell proliferation was diminished in coculture experiments. When transferred into EAE mice, DC-CQ was able to reduce the clinical manifestation of the disease through the modulation of the immune response against neuroantigens. The data presented herein indicate that chloroquine-mediated modulation of the immune system is achieved by a direct effect on DCs and that DC-CQ adoptive transfer may be a promising approach for avoiding drug toxicity.