The Francis Crick Institute
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The dietary sweetener sucralose is a negative modulator of T cell-mediated responses.

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journal contribution
posted on 2023-04-06, 10:35 authored by Fabio Zani, Julianna Blagih, Tim Gruber, Michael D Buck, Nicholas Jones, Marc Hennequart, Clare L Newell, Steven E Pilley, Pablo Soro-Barrio, Gavin Kelly, Nathalie M Legrave, Eric C Cheung, Ian S Gilmore, Alex P Gould, Cristina Garcia-Caceres, Karen H Vousden
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 sweeteners2-5. 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.


Crick (Grant ID: CC2073, Grant title: Vousden CC2073) Crick (Grant ID: CC2101, Grant title: Gould CC2101) Crick (Grant ID: CC1107, Grant title: STP Bioinformatics & Biostatistics) Crick (Grant ID: CC1067, Grant title: STP Metabolomics) Crick (Grant ID: CC2090, Grant title: Reis e Sousa CC2090) Cancer Research UK (Grant ID: 26855, Grant title: CRUK C596/A26855) European Commission (Grant ID: 837951 - DC Metabolism, Grant title: EC 837951 - DC Metabolism)