鼠李糖乳杆菌GG通过SLC5A12介导小鼠Th17/Treg细胞平衡缓解结肠炎
{"_":" GG Alleviates Colitis by SLC5A12-Mediated Th17/Treg Cell Balance in Mice.","i":["Lactobacillus rhamnosus"]}
摘要(中文译文)
鼠李糖乳杆菌GG（LGG）是应用最广泛的益生菌菌株之一，具有多种生物学功能，包括预防和治疗胃肠道感染以及调节免疫应答。本研究探讨了LGG在调节初始CD4 T细胞分化中的作用及其对缓解葡聚糖硫酸钠（DSS）诱导的小鼠结肠炎的影响。体外实验表明，LGG来源的代谢产物不仅促进初始CD4 T细胞向辅助性T细胞17（Th17细胞）分化，还选择性上调乳酸特异性转运体溶质载体家族5成员12（SLC5A12）的表达。有趣的是，我们通过CD4 T细胞-单核细胞共培养模型发现，负载热灭活LGG的单核细胞可调节初始CD4 T细胞优先向Treg细胞而非Th17细胞分化。为解释上述矛盾现象，我们采用实验性结肠炎模型，发现LGG给药可缓解小鼠DSS诱导的结肠炎，表现为体重减轻和疾病活动指数下降。此外，阻断SLC5A12（使用特异性抗体）进一步降低了结肠组织学炎症评分，并减少了促炎细胞因子如IFN-γ、IL-6、IL-17F和IL-21的分泌。值得注意的是，阻断SLC5A12消除了LGG诱导的IL-17⁺CD4 T（Th17）细胞分化，但显著增加了结肠固有层中Foxp3⁺CD4 T（Treg）细胞的比例。此外，与其他组相比，从LGG治疗的结肠炎小鼠中分离的结肠CD4 T细胞内乳酸浓度更高。另外，我们还发现仅DSS处理小鼠的结肠组织中氧化应激指标如MDA和H₂O₂水平升高，活性氧（ROS）过量，而LGG可通过诱导肠上皮细胞中核因子E2相关因子2（Nrf2）的表达来清除ROS。总之，这些结果表明LGG可能通过调节Th17/Treg平衡来缓解临床前结肠炎，而阻断SLC5A12似乎可增强LGG的抗炎特性。
Abstract
: GG (LGG) is one of the most widely utilized probiotic strains with a variety of biological functions including prevention and treatment of gastro-intestinal infections and regulation of immune responses. : Here, we explored the role of LGG in regulating the differentiation of naïve CD4 T cells and its effect on alleviating the dextran sulfate sodium (DSS)-induced colitis in mice. : In vitro, we showed that LGG-derived metabolites not only promoted the differentiation of naive CD4 T cells into T-helper 17 cells (Th17 cells), but also selectively upregulated the expression of lactate-specific transporter solute carrier family 5 member 12 (SLC5A12). Interestingly, we manipulated a CD4 T cell-monocytes co-culture and found that heated LGG-loaded monocytes modulate naive CD4 T cells to differentiate preferentially into Treg cells rather than Th17 cells. To explain the above-mentioned contradiction, we used an experimental colitis model and found that LGG administration alleviated the DSS-induced colitis in mice, as indicated by decreases in weight loss and disease activity index. Moreover, SLC5A12 blockade (using a specific antibody) further reduced the colonic histological inflammatory score and decreased secretion of proinflammatory cytokines such as IFN-γ, IL-6, IL-17F, and IL-21. Notably, SLC5A12 blockade abolished the LGG-induced differentiation of the IL-17CD4 T (Th17) cells but significantly increased the frequency of Foxp3CD4 T (Treg) cells in the colonic lamina propria. Furthermore, a higher intracellular lactate concentration was observed in the colonic CD4 T cells isolated from the LGG-treated colitic mice compared with other groups. Additionally, we also found elevated levels of oxidative stress indicators such as MDA and HO, as well as excessive reactive oxygen species (ROS) in colonic tissue of DSS-treated only mice, while LGG can scavenge ROS by inducing nuclear factor-erythroid 2-related factor 2 (Nrf2) expression in enterocytes. : Altogether, these results indicate that LGG might alleviate preclinical colitis by modulating the Th17/Treg balance, and SLC5A12 blockade appears to enhance the anti-inflammatory properties of LGG.
如何引用
AMA
Yiling Zhang, Xianghong He, Qian Zhao, Qiming Duan, Heping Li, Rui Qin, et al. {"_":" GG Alleviates Colitis by SLC5A12-Mediated Th17/Treg Cell Balance in Mice.","i":["Lactobacillus rhamnosus"]}. Nutrients. 2026; doi:10.3390/nu18111724.
APA
Yiling Zhang, Xianghong He, Qian Zhao, Qiming Duan, Heping Li, Rui Qin, et al (2026). {"_":" GG Alleviates Colitis by SLC5A12-Mediated Th17/Treg Cell Balance in Mice.","i":["Lactobacillus rhamnosus"]}. Nutrients. https://doi.org/10.3390/nu18111724
GB/T 7714
Yiling Zhang, Xianghong He, Qian Zhao, Qiming Duan, Heping Li, Rui Qin, et al. {"_":" GG Alleviates Colitis by SLC5A12-Mediated Th17/Treg Cell Balance in Mice.","i":["Lactobacillus rhamnosus"]}[J]. Nutrients, 2026 doi:10.3390/nu18111724.
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