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首页> 外文期刊>Clinical & developmental immunology. >Protection against Autoimmune Diabetes by Silkworm-Produced GFP-Tagged CTB-Insulin Fusion Protein
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Protection against Autoimmune Diabetes by Silkworm-Produced GFP-Tagged CTB-Insulin Fusion Protein

机译：蚕产生的带有GFP标签的CTB-胰岛素融合蛋白对自身免疫性糖尿病的保护

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In animals, oral administration of the cholera toxin B (CTB) subunit conjugated to the autoantigen insulin enhances the specific immune-unresponsive state. This is called oral tolerance and is capable of suppressing autoimmune type 1 diabetes (T1D). However, the process by which the CTB-insulin (CTB-INS) protein works as a therapy for T1D in vivo remains unclear. Here, we successfully expressed a green fluorescent protein- (GFP-) tagged CTB-Ins (CTB-Ins-GFP) fusion protein in silkworms in a pentameric form that retained the native ability to activate the mechanism. Oral administration of the CTB-Ins-GFP protein induced special tolerance, delayed the development of diabetic symptoms, and suppressed T1D onset in nonobese diabetic (NOD) mice. Moreover, it increased the numbers of CD4~(+)CD25~(+)Foxp3~(+)T regulatory (Treg) cells in peripheral lymph tissues and affected the biological activity of spleen cells. This study demonstrated that the CTB-Ins-GFP protein produced in silkworms acted as an oral protein vaccine, inducing immunological tolerance involving CD4~(+)CD25~(+)Foxp3~(+)Treg cells in treating T1D.
机译：在动物中，口服与自身抗原胰岛素缀合的霍乱毒素B（CTB）亚基可增强特定的免疫无反应状态。这被称为口服耐受，并且能够抑制自身免疫性1型糖尿病（T1D）。但是，CTB胰岛素（CTB-INS）蛋白作为体内T1D疗法的过程尚不清楚。在这里，我们以五聚体形式成功地在蚕中表达了绿色荧光蛋白-（GFP-）标签的CTB-Ins（CTB-Ins-GFP）融合蛋白，该蛋白保留了激活该机制的天然能力。在非肥胖糖尿病（NOD）小鼠中，口服CTB-Ins-GFP蛋白诱导了特殊的耐受性，延迟了糖尿病症状的发展，并抑制了T1D发作。此外，它增加了外周淋巴组织中CD4〜（+）CD25〜（+）Foxp3〜（+）T调节（Treg）细胞的数量，并影响了脾细胞的生物学活性。这项研究表明，家蚕中产生的CTB-Ins-GFP蛋白可作为口服蛋白疫苗，诱导涉及CD4〜（+）CD25〜（+）Foxp3〜（+）Treg细胞的免疫耐受，从而治疗T1D。

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