Chloroquine treatment enhances regulatory T cells and reduces the severity of experimental autoimmune encephalomyelitis.
Chloroquine treatment enhances regulatory T cells and reduces the severity of experimental autoimmune encephalomyelitis.
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DOI：
10.1371/journal.pone.0065913
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Verinaud L
中科院分区：
文献类型：
--
作者：
Thomé R;Moraes AS;Bombeiro AL;Farias Ados S;Francelin C;da Costa TA;Di Gangi R;dos Santos LM;de Oliveira AL;Verinaud L
炎症过程的调节是防止有害反应和自身免疫性疾病发展的必要步骤，主要由调节性T（Treg）细胞和抑制性树突状细胞（DC）协调。专注于Treg细胞的过继转移或其体内扩增的疗法在几种实验模型中控制炎症方面取得了巨大成功。氯喹（CQ），一种抗疟疾药物，被证明可以减少炎症，尽管其机制仍然不清楚。在这种情况下，我们的目的是评估氯喹治疗是否改变了正常小鼠中Treg细胞和DC的频率。此外，还研究了CQ对实验性自身免疫性脑脊髓炎（EAE）（人类多发性硬化的实验模型）的预防性和治疗性处理的效果。用髓鞘少突胶质细胞糖蛋白（MOG 35 -55）肽免疫C57 BL/6小鼠诱导EAE。C57 BL/6小鼠腹腔注射氯喹。结果显示CQ处理引起Treg细胞频率的增加以及DC的减少。我们接下来评估了预防性CQ给药是否能够减少EAE的临床和组织病理学体征。我们的结果表明，与对照组相比，CQ处理的小鼠发生了轻度EAE，这与中枢神经系统中炎性细胞浸润减少和Treg细胞频率增加有关。此外，MOG 35 -55反应性T细胞的增殖被氯喹处理显著抑制。在发病后给予氯喹也观察到类似的结果。我们首次表明CQ治疗促进Treg细胞的扩增，证实了先前的报告表明氯喹具有免疫调节特性。我们的研究结果还表明，CQ治疗抑制炎症中枢神经系统的EAE造成的小鼠，无论是在预防和治疗方法。我们假设CQ治疗诱导的调节性T细胞数量的增加与EAE临床体征的减少有关。
The modulation of inflammatory processes is a necessary step, mostly orchestrated by regulatory T (Treg) cells and suppressive Dendritic Cells (DCs), to prevent the development of deleterious responses and autoimmune diseases. Therapies that focused on adoptive transfer of Treg cells or their expansion in vivo achieved great success in controlling inflammation in several experimental models. Chloroquine (CQ), an anti-malarial drug, was shown to reduce inflammation, although the mechanisms are still obscure. In this context, we aimed to access whether chloroquine treatment alters the frequency of Treg cells and DCs in normal mice. In addition, the effects of the prophylactic and therapeutic treatment with CQ on Experimental Autoimmune Encephalomyelitis (EAE), an experimental model for human Multiple Sclerosis, was investigated as well. EAE was induced in C57BL/6 mice by immunization with myelin oligodendrocyte glycoprotein (MOG35–55) peptide. C57BL/6 mice were intraperitoneally treated with chloroquine. Results show that the CQ treatment provoked an increase in Treg cells frequency as well as a decrease in DCs. We next evaluated whether prophylactic CQ administration is capable of reducing the clinical and histopathological signs of EAE. Our results demonstrated that CQ-treated mice developed mild EAE compared to controls that was associated with lower infiltration of inflammatory cells in the central nervous system CNS) and increased frequency of Treg cells. Also, proliferation of MOG35–55-reactive T cells was significantly inhibited by chloroquine treatment. Similar results were observed when chloroquine was administrated after disease onset. We show for the first time that CQ treatment promotes the expansion of Treg cells, corroborating previous reports indicating that chloroquine has immunomodulatory properties. Our results also show that CQ treatment suppress the inflammation in the CNS of EAE-inflicted mice, both in prophylactic and therapeutic approaches. We hypothesized that the increased number of regulatory T cells induced by the CQ treatment is involved in the reduction of the clinical signs of EAE.
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影响因子：
27.4
作者：
Grierson, DJ
通讯作者：
Grierson, DJ
影响因子：
4.9
作者：
Bilsen JV;Lard L;der Voort EV;Elferink D;Bakker A;Dongen HV;Miltenburg A;Huizinga T;Vries RD;Toes R
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Toes R
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Krishnamoorthy G
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9.3
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Fissolo N;Costa C;Nurtdinov RN;Bustamante MF;Llombart V;Mansilla MJ;Espejo C;Montalban X;Comabella M
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Comabella M
影响因子：
3.7
作者：
Corthay A
通讯作者：
Corthay A