英国弗朗西斯·克里克研究所Karen H. Vousden，Julianna Blagih和Fabio Zani共同合作，近期取得重要工作进展。他们研究发现膳食甜味剂三氯蔗糖是 T 细胞介导反应的负调节因子。相关研究成果2023年3月15日在线发表于发表于《自然》杂志上。

据介绍，人工甜味剂被用作许多食品中的无热量代糖，其消费量在过去几年中大幅增加。尽管人们普遍认为这是安全的，但人们对食用某些甜味剂的长期安全性表示担忧。

研究人员表明，小鼠摄入高剂量三氯蔗糖通过限制T细胞增殖和T细胞分化产生免疫调节作用。从机制上讲，三氯蔗糖影响T细胞的膜秩序，同时降低T细胞受体信号传导和细胞内钙动员的效率。在皮下癌症模型和细菌感染模型中，给予三氯蔗糖的小鼠表现出CD8⁺ T细胞抗原特异性反应降低，在T细胞介导的自身免疫模型中表现出T细胞功能降低。

总的来说，这些发现表明，大量摄入三氯蔗糖可以抑制T细胞介导的反应，这种作用可以用于缓解T细胞依赖性自身免疫性疾病。

附：英文原文

Title: The dietary sweetener sucralose is a negative modulator of T cell-mediated responses

Author: Zani, Fabio, Blagih, Julianna, Gruber, Tim, Buck, Michael D., Jones, Nicholas, Hennequart, Marc, Newell, Clare L., Pilley, Steven E., Soro-Barrio, Pablo, Kelly, Gavin, Legrave, Nathalie M., Cheung, Eric C., Gilmore, Ian S., Gould, Alex P., Garcia-Caceres, Cristina, Vousden, Karen H.

Issue&Volume: 2023-03-15

Abstract: Artificial sweeteners are used as calorie-free sugar substitutes in many food products and their consumption has increased substantially over the past years1. Although generally regarded as safe, some concerns have been raised about the long-term safety of the consumption of certain sweeteners2,3,4,5. In this study, we show that the intake of high doses of sucralose in mice results in immunomodulatory effects by limiting T cell proliferation and T cell differentiation. Mechanistically, sucralose affects the membrane order of T cells, accompanied by a reduced efficiency of T cell receptor signalling and intracellular calcium mobilization. Mice given sucralose show decreased CD8+ T cell antigen-specific responses in subcutaneous cancer models and bacterial infection models, and reduced T cell function in models of T cell-mediated autoimmunity. Overall, these findings suggest that a high intake of sucralose can dampen T cell-mediated responses, an effect that could be used in therapy to mitigate T cell-dependent autoimmune disorders.

DOI: 10.1038/s41586-023-05801-6

Source: https://www.nature.com/articles/s41586-023-05801-6