School of Life Sciences and Immune Synapse Research Center, Gwangju Institute of Science and Technology (GIST), Buk-gu, Gwangju, Korea.
PLoS One. 2012;7(12):e52119. doi: 10.1371/journal.pone.0052119. Epub 2012 Dec 20.
Probiotics are live bacteria that confer health benefits to the host physiology. Although protective role of probiotics have been reported in diverse diseases, no information is available whether probiotics can modulate neuromuscular immune disorders. We have recently demonstrated that IRT5 probiotics, a mixture of 5 probiotics, could suppress diverse experimental disorders in mice model. In this study we further investigated whether IRT5 probiotics could modulate the progression of experimental autoimmune myasthenia gravis (EAMG). Myasthenia gravis (MG) is a T cell dependent antibody mediated autoimmune disorder in which acetylcholine receptor (AChR) at the neuromuscular junction is the major auto-antigen. Oral administration of IRT5 probiotics significantly reduced clinical symptoms of EAMG such as weight loss, body trembling and grip strength. Prophylactic effect of IRT5 probiotics on EMAG is mediated by down-regulation of effector function of AChR-reactive T cells and B cells. Administration of IRT5 probiotics decreased AChR-reactive lymphocyte proliferation, anti-AChR reactive IgG levels and inflammatory cytokine levels such as IFN-γ, TNF-α, IL-6 and IL-17. Down-regulation of inflammatory mediators in AChR-reactive lymphocytes by IRT5 probiotics is mediated by the generation of regulatory dendritic cells (rDCs) that express increased levels of IL-10, TGF-β, arginase 1 and aldh1a2. Furthermore, DCs isolated from IRT5 probiotics-fed group effectively converted CD4(+) T cells into CD4(+)Foxp3(+) regulatory T cells compared with control DCs. Our data suggest that IRT5 probiotics could be applicable to modulate antibody mediated autoimmune diseases including myasthenia gravis.
益生菌是对宿主生理有益的活菌。虽然益生菌在多种疾病中都有保护作用，但目前尚不清楚益生菌是否可以调节神经肌肉免疫紊乱。我们最近证明，IRT5 益生菌（由 5 种益生菌混合而成）可以抑制小鼠模型中的多种实验性疾病。在这项研究中，我们进一步研究了 IRT5 益生菌是否可以调节实验性自身免疫性重症肌无力（EAMG）的进展。重症肌无力（MG）是一种 T 细胞依赖性抗体介导的自身免疫性疾病，其中神经肌肉接头的乙酰胆碱受体（AChR）是主要的自身抗原。IRT5 益生菌的口服给药显著减轻了 EAMG 的临床症状，如体重减轻、身体颤抖和握力。IRT5 益生菌对 EMAG 的预防作用是通过下调 AChR 反应性 T 细胞和 B 细胞的效应功能来介导的。IRT5 益生菌的给药减少了 AChR 反应性淋巴细胞的增殖、抗 AChR 反应性 IgG 水平以及炎症细胞因子水平，如 IFN-γ、TNF-α、IL-6 和 IL-17。IRT5 益生菌下调 AChR 反应性淋巴细胞中的炎症介质是通过产生表达高水平 IL-10、TGF-β、精氨酸酶 1 和 aldh1a2 的调节树突状细胞（rDCs）来介导的。此外，与对照组 DC 相比，来自 IRT5 益生菌喂养组的 DC 有效地将 CD4(+)T 细胞转化为 CD4(+)Foxp3(+)调节性 T 细胞。我们的数据表明，IRT5 益生菌可用于调节包括重症肌无力在内的抗体介导的自身免疫性疾病。
