Recombinant Lactococcus lactis Carrying IL-4 and IL-10 Coding Vectors Protects against Type 1 Diabetes in NOD Mice and Attenuates Insulitis in the STZ-Induced Model.
Recombinant Lactococcus lactis Carrying IL-4 and IL-10 Coding Vectors Protects against Type 1 Diabetes in NOD Mice and Attenuates Insulitis in the STZ-Induced Model.
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DOI：
10.1155/2021/6697319
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发表时间：
2021
影响因子：
4.3
通讯作者：
Miyoshi A
中科院分区：
文献类型：
--
作者：
Preisser TM;da Cunha VP;Santana MP;Pereira VB;Cara DC;Souza BM;Miyoshi A
1型糖尿病（T1 D）是一种自身免疫性疾病，其最终导致胰腺中的β细胞破坏，随后导致胰岛素产生不足。细胞因子在糖尿病的发展中起着至关重要的作用，协调免疫细胞的招募和行动，不仅破坏胰岛素产生细胞，而且保护它们。因此，本研究的目的是研究口服乳酸乳球菌MG 1363 FnBPA+菌株携带编码IL-4和IL-10的质粒在链脲佐菌素（STZ-）诱导的糖尿病模型和非肥胖糖尿病（NOD）小鼠中的作用。用携带编码IL-4和IL-10的质粒的组合细菌菌株治疗STZ诱导的小鼠，与接受单独细菌菌株的小鼠相比，显示出更低的糖尿病发病率和更多的胰岛保存。L.乳酸菌MG 1363 FnBPA+（pValac：：dts：：IL-4）和乳酸菌L.乳酸菌MG 1363 FnBPA+（pValac：：IL-10）导致NOD小鼠中针对糖尿病的保护。结果表明，口服重组细菌的联合治疗可以预防NOD小鼠的高血糖，减少胰岛的破坏。此外，血清和胰腺组织中IL-4和IL-10水平的增加揭示了治疗的全身效应，也有利于抗炎微环境。胰腺中IL-12浓度的降低对于炎症的调节是必不可少的，导致在治疗的NOD小鼠中没有糖尿病的发生。长期使用L.携带编码IL-4和IL-10的质粒的乳酸菌菌株表明口服耐受性的发展，并证实了这种粘膜递送的有效工具的使用。第一次，L。在STZ诱导的和NOD小鼠模型中测试携带编码IL-4和IL-10的真核表达载体的乳酸菌MG 1363 FnBPA+菌株。因此，我们的研究表明，这种创新策略为T1 D和其他自身免疫性疾病的进一步研究提供了免疫调节潜力。
Type 1 diabetes (T1D) is an autoimmune disease that culminates in beta cell destruction in the pancreas and, subsequently, deficiency in insulin production. Cytokines play a crucial role in the development of diabetes, orchestrating the recruitment and action of immune cells, to not only destroy insulin-producing cells but also preserve them. Therefore, the aim of this study was to investigate the effect of orally administered Lactococcus lactis MG1363 FnBPA+ strains carrying plasmids encoding IL-4 and IL-10 in the streptozotocin- (STZ-) induced diabetes model and in nonobese diabetic (NOD) mice. The STZ-induced mice that were treated with combined bacterial strains carrying plasmids encoding IL-4 and IL-10 showed lower incidence of diabetes and more preserved pancreatic islets than the mice that received the individual bacterial strains. Combined administration of L. lactis MG1363 FnBPA+ (pValac::dts::IL-4) and L. lactis MG1363 FnBPA+ (pValac::IL-10) resulted in protection against diabetes in NOD mice. It was shown that the combined treatment with recombinant bacterial by oral route prevented hyperglycemia and reduced the pancreatic islets-destruction in NOD mice. In addition, increased levels of IL-4 and IL-10 in serum and pancreatic tissue revealed a systemic effect of the treatment and also favored an anti-inflammatory microenvironment. Reduced concentrations of IL-12 in pancreas were essential to the regulation of inflammation, resulting in no incidence of diabetes in treated NOD mice. Normal levels of intestinal sIgA after long-term treatment with the L. lactis strains carrying plasmids encoding IL-4 and IL-10 indicate the development of oral tolerance and corroborate the use of this potent tool of mucosal delivery. For the first time, L. lactis MG1363 FnBPA+ strains carrying eukaryotic expression vectors encoding IL-4 and IL-10 are tested in STZ-induced and NOD mouse models. Therefore, our study demonstrates this innovative strategy provides immunomodulatory potential for further investigations in T1D and other autoimmune diseases.
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影响因子：
5.2
作者：
Burrack AL;Martinov T;Fife BT
通讯作者：
Fife BT
影响因子：
0.7
作者：
Del Carmen, S.;Zurita-Turk, M.;LeBlanc, J. G.
通讯作者：
LeBlanc, J. G.
影响因子：
5.1
作者：
Koh, JJ;Ko, KS;Kim, SW
通讯作者：
Kim, SW
乳酸乳酸作为耐受性免疫疗法的多功能载体。
影响因子：
7.3
作者：
Cook DP;Gysemans C;Mathieu C
通讯作者：
Mathieu C
影响因子：
4.6
作者：
daRosa, L. C.;Chiuso-Minicucci, F.;Sartori, A.
通讯作者：
Sartori, A.