HSP65 serves as an immunogenic carrier for a diabetogenic peptide P277 inducing anti-inflammatory immune response in NOD mice by nasal administration

HSP65 serves as an immunogenic carrier for a diabetogenic peptide P277 inducing anti-inflammatory immune response in NOD mice by nasal administration
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HSP65 作为致糖尿病肽 P277 的免疫原性载体,通过鼻腔给药诱导 NOD 小鼠抗炎免疫反应

DOI:
10.1016/j.vaccine.2010.02.100
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发表时间:
2010-04-26
期刊:
影响因子:
5.5
通讯作者:
Liu Jingjing
Liu Jingjing
中科院分区:
医学3区
文献类型:
--
作者:
Jin Liang;Zhu Aihua;Liu Jingjing

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在多种自身免疫模型中,例如关节炎和动脉粥样硬化,粘膜施用自身抗原1451,65可以诱导抗炎免疫反应,并减少器官特异性炎症和疾病。我们一直对HSP65作为致糖尿病肽P277的免疫原性载体感兴趣,也可以通过粘膜施用在NOD小鼠中诱导抗炎免疫反应。因此,HSP65抗1型糖尿病的双重功能和将获得P277 为了检验这一假设,我们检查了在没有佐剂的情况下鼻内接种HSP65携带的P277串联重复序列对NOD小鼠自身免疫性糖尿病的影响。我们发现,糖尿病的发病率显着降低,胰岛炎受到抑制,P277 的 IgG2a 同种型抗体以及促炎细胞因子 IFN-γ 和 IL-2 的分泌减少,P277 的 IgG1、IgG2b 亚类抗体以及抗炎细胞因子 IL-10 和 IL-4 的分泌增加,鼻腔施用融合蛋白 HSP65-6 x P277 的增殖减少。我们的结果表明,HSP65 可以作为基于P277的疫苗和粘膜给药的特别有利的载体可能是治疗1型糖尿病的治疗方法。 (C) 2010 Elsevier Ltd. 版权所有
Mucosal administration of autoantigen 1451,65 can induce anti-inflammatory immune response and decrease organ-specific inflammation and disease in several models of autoimmunity, such as arthritis and atherosclerosis We have been interested in whether the HSP65 serves as an immunogenic carrier for a diabetogenic peptide P277 can also Induce anti-inflammatory immune response in NOD mice by mucosal administration Thus, the dual functions of anti-type 1 diabetes of HSP65 and P277 will be obtained To test this hypothesis, we examined the effect of intranasal vaccination with P277 tandem repeat sequences carried by HSP65 in the absence of adjuvants on autoimmune diabetes in NOD mice. We found a significant decrease in the incidence of diabetes, inhibition of insulitis, reduction in IgG2a isotype antibodies to P277 and proinflammatory cytokines IFN-gamma and IL-2 secretion, increased IgG1, IgG2b subclass antibodies to P277 and anti-inflammatory cytokmes IL-10 and IL-4 secretion, and reduced proliferation in nasal administration of the fusion protein HSP65-6 x P277 Our results demonstrate that HSP65 may serve as a particularly advantageous carrier for P277-based vaccines and mucosal administration may be a therapeutic approach for treatment of type 1 diabetes. (C) 2010 Elsevier Ltd. All rights reserved