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

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 and Karen H. Vousden ()
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Fabio Zani: The Francis Crick Institute
Julianna Blagih: The Francis Crick Institute
Tim Gruber: Helmholtz Zentrum München and German Center for Diabetes Research (DZD)
Michael D. Buck: The Francis Crick Institute
Nicholas Jones: Swansea University Medical School, Swansea University
Marc Hennequart: The Francis Crick Institute
Clare L. Newell: National Physical Laboratory
Steven E. Pilley: The Francis Crick Institute
Pablo Soro-Barrio: The Francis Crick Institute
Gavin Kelly: The Francis Crick Institute
Nathalie M. Legrave: The Francis Crick Institute
Eric C. Cheung: The Francis Crick Institute
Ian S. Gilmore: National Physical Laboratory
Alex P. Gould: The Francis Crick Institute
Cristina Garcia-Caceres: Helmholtz Zentrum München and German Center for Diabetes Research (DZD)
Karen H. Vousden: The Francis Crick Institute

Nature, 2023, vol. 615, issue 7953, 705-711

Abstract: 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 sweeteners2–5. 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.

Date: 2023
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DOI: 10.1038/s41586-023-05801-6

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