Treatment with MOG-DNA vaccines induces CD4+CD25+FoxP3+ regulatory T cells and up-regulates genes with neuroprotective functions in experimental autoimmune encephalomyelitis.
Treatment with MOG-DNA vaccines induces CD4+CD25+FoxP3+ regulatory T cells and up-regulates genes with neuroprotective functions in experimental autoimmune encephalomyelitis.
复制标题
DOI：
10.1186/1742-2094-9-139
复制
发表时间：
2012-06-22
影响因子：
9.3
通讯作者：
Comabella M
中科院分区：
文献类型：
--
作者：
Fissolo N;Costa C;Nurtdinov RN;Bustamante MF;Llombart V;Mansilla MJ;Espejo C;Montalban X;Comabella M
DNA疫苗代表了自身免疫性疾病如多发性硬化症（MS）的有前途的治疗策略。然而，DNA疫苗诱导免疫调节的确切机制在很大程度上仍然未知。在这里，我们的目的是扩大现有的知识在MS的动物模型，实验性自身免疫性脑脊髓炎（EAE）的DNA疫苗的作用机制，通过治疗EAE小鼠编码的髓鞘少突胶质细胞糖蛋白（MOG），并探讨对疾病引起的炎症和神经退行性变化的治疗效果。通过用MOG 35 -55肽免疫在C57 BL 6/J小鼠中诱导EAE。在预防和治疗方法中，用MOG-DNA疫苗或媒介物肌内处理小鼠。在中枢神经系统（CNS）组织中进行组织学研究。通过流式细胞术实现细胞因子产生和调节性T细胞（Treg）定量。使用微阵列确定基因表达模式，并通过实时PCR验证主要结果。当在预防和治疗环境中施用时，MOG-DNA治疗减少了EAE的临床和组织病理学体征。临床EAE的抑制与抗原（Ag）特异性促炎性Th 1和Th 17免疫应答的抑制有关，有趣的是，外周Treg的扩增和CNS中编码神经营养因子和参与髓鞘再生的蛋白质的基因的上调有关。这些结果首次表明，DNA疫苗在EAE中的有益作用不仅限于抗炎机制，DNA疫苗还可能通过迄今未知的神经保护机制发挥积极作用。
DNA vaccines represent promising therapeutic strategies in autoimmune disorders such as multiple sclerosis (MS). However, the precise mechanisms by which DNA vaccines induce immune regulation remain largely unknown. Here, we aimed to expand previous knowledge existing on the mechanisms of action of DNA vaccines in the animal model of MS, experimental autoimmune encephalomyelitis (EAE), by treating EAE mice with a DNA vaccine encoding the myelin oligodendrocyte glycoprotein (MOG), and exploring the therapeutic effects on the disease-induced inflammatory and neurodegenerative changes. EAE was induced in C57BL6/J mice by immunization with MOG35-55 peptide. Mice were intramuscularly treated with a MOG-DNA vaccine or vehicle in prophylactic and therapeutic approaches. Histological studies were performed in central nervous system (CNS) tissue. Cytokine production and regulatory T cell (Treg) quantification were achieved by flow cytometry. Gene expression patterns were determined using microarrays, and the main findings were validated by real-time PCR. MOG-DNA treatment reduced the clinical and histopathological signs of EAE when administered in both prophylactic and therapeutic settings. Suppression of clinical EAE was associated with dampening of antigen (Ag)-specific proinflammatory Th1 and Th17 immune responses and, interestingly, expansion of Treg in the periphery and upregulation in the CNS of genes encoding neurotrophic factors and proteins involved in remyelination. These results suggest for the first time that the beneficial effects of DNA vaccines in EAE are not limited to anti-inflammatory mechanisms, and DNA vaccines may also exert positive effects through hitherto unknown neuroprotective mechanisms.
登录
查看更多内容
影响因子：
64.8
作者：
Bettelli, E;Carrier, YJ;Kuchroo, VK
通讯作者：
Kuchroo, VK
影响因子：
5.4
作者：
Haas, J;Hug, A;Wildemann, B
通讯作者：
Wildemann, B
DOI：
10.1084/jem.20051409
发表时间：
2005-11-21
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Chen Z;Herman AE;Matos M;Mathis D;Benoist C
通讯作者：
Benoist C
影响因子：
--
作者：
Bar-Or, Amit;Vollmer, Timothy;Garren, Hideki
通讯作者：
Garren, Hideki
影响因子：
3.5
作者：
Ho, Peggy P.;Higgins, John P.;Robinson, William H.
通讯作者：
Robinson, William H.