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用氯喹处理的树突状细胞可调节实验性自身免疫性脑脊髓炎。

Dendritic cells treated with chloroquine modulate experimental autoimmune encephalomyelitis.

作者信息

Thomé Rodolfo, Issayama Luidy Kazuo, DiGangi Rosaria, Bombeiro Andre Luis, da Costa Thiago Alves, Ferreira Isadora Tassinari, de Oliveira Alexandre Leite Rodrigues, Verinaud Liana

机构信息

Department of Structural and Functional Biology, Institute of Biology, State University of Campinas, Campinas, Brazil.

出版信息

Immunol Cell Biol. 2014 Feb;92(2):124-32. doi: 10.1038/icb.2013.73. Epub 2013 Nov 12.

Abstract

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.

摘要

氯喹(CQ)是一种抗疟药物,已被证明可调节免疫系统并减轻实验性自身免疫性脑脊髓炎(EAE)的严重程度。疾病抑制机制依赖于调节性T细胞的诱导,尽管也存在不依赖调节性T细胞的机制。我们旨在评估CQ是否能够在表型和功能上调节骨髓来源的树突状细胞(DC),以及CQ调节的DC转移是否能减轻EAE病程。我们的结果表明,经CQ处理的DC呈现出改变的超微结构形态以及参与抗原呈递的分子表达降低。因此,在共培养实验中T细胞增殖减少。当将DC-CQ转移到EAE小鼠体内时,它能够通过调节针对神经抗原的免疫反应来减轻疾病的临床表现。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过继转移可能是一种避免药物毒性的有前景的方法。

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