Applications of Genetically Modified Immunobiotics with High Immunoregulatory Capacity for Treatment of Inflammatory Bowel Diseases.

Applications of Genetically Modified Immunobiotics with High Immunoregulatory Capacity for Treatment of Inflammatory Bowel Diseases.
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具有高免疫调节能力的转基因免疫生物的应用,用于治疗炎症性肠病。

DOI:
10.3389/fimmu.2017.00022
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发表时间:
2017
影响因子:
7.3
通讯作者:
Shimosato T
Shimosato T
中科院分区:
医学2区
文献类型:
--
作者:
Shigemori S;Shimosato T

文献摘要

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炎症性肠病(IBD),包括溃疡性结肠炎和克罗恩病,是以胃肠道免疫反应失调为特征的慢性炎症性疾病。近年来,IBD在发达国家的发病率有所上升,但其预防/治疗方法尚未确立。使用转基因益生菌定点传递显示抗炎特性的分子显示出作为预防和治疗IBD的新策略的前景。转基因益生菌的优势包括(1)能够使用细菌作为载体,使人类能够安全和长期使用;(2)减少副作用的风险;(3)降低成本。使用乳酸乳球菌的肠道输送抗炎蛋白,如细胞因子和酶,已被证明可以调节宿主肠道的动态平衡,这取决于所输送的蛋白质特定的机制。此外,使用分泌白介素10的LC的临床经验。乳酸已被证明是安全的,并有助于IBD治疗中的生物遏制。另一方面,一些临床前研究表明,由于细菌本身的免疫调节作用和所提供的重组蛋白的抗炎作用之间的协同作用,免疫生物素的转基因菌株(能够有益地调节粘膜免疫的益生菌菌株)对肠道炎症提供了有益的效果。在这篇综述中,我们讨论了利用具有免疫调节作用的转基因益生菌(转基因免疫生物素)预防和治疗IBD的策略的快速进展。特别是,我们讨论了用作递送剂的菌株的类型。
Inflammatory bowel diseases (IBDs), including ulcerative colitis and Crohn’s disease, are chronic inflammatory diseases characterized by dysregulated immune responses of the gastrointestinal tract. In recent years, the incidence of IBDs has increased in developed nations, but their prophylaxis/treatment is not yet established. Site-directed delivery of molecules showing anti-inflammatory properties using genetically modified (gm)-probiotics shows promise as a new strategy for the prevention and treatment of IBD. Advantages of gm-probiotics include (1) the ability to use bacteria as a delivery vehicle, enabling safe and long-term use by humans, (2) decreased risks of side effects, and (3) reduced costs. The intestinal delivery of anti-inflammatory proteins such as cytokines and enzymes using Lactococcus lactis has been shown to regulate host intestinal homeostasis depending on the delivered protein-specific machinery. Additionally, clinical experience using interleukin 10-secreting Lc. lactis has been shown to be safe and to facilitate biological containment in IBD therapy. On the other hand, some preclinical studies have demonstrated that gm-strains of immunobiotics (probiotic strains able to beneficially regulate the mucosal immunity) provide beneficial effects on intestinal inflammation as a result of the synergy between the immunoregulatory effects of the bacterium itself and the anti-inflammatory effects of the delivered recombinant proteins. In this review, we discuss the rapid progression in the development of strategies for the prophylaxis and treatment of IBD using gm-probiotics that exhibit immune regulation effects (gm-immunobiotics). In particular, we discuss the type of strains used as delivery agents.