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

Artificial sweeteners are used as calorie-free sugar substitutes in many food products and their consumption has increased substantially over the past years(1). Although generally regarded as safe, some concerns have been raised about the long-term safety of the consumption of certain sweeteners(2–5...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10033444/
https://www.ncbi.nlm.nih.gov/pubmed/36922598
http://dx.doi.org/10.1038/s41586-023-05801-6
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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.
author_facet 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.
author_sort Zani, Fabio
collection PubMed
description Artificial sweeteners are used as calorie-free sugar substitutes in many food products and their consumption has increased substantially over the past years(1). Although generally regarded as safe, some concerns have been raised about the long-term safety of the consumption of certain sweeteners(2–5). 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.
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spelling pubmed-100334442023-03-24 The dietary sweetener sucralose is a negative modulator of T cell-mediated responses 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. Nature Article Artificial sweeteners are used as calorie-free sugar substitutes in many food products and their consumption has increased substantially over the past years(1). Although generally regarded as safe, some concerns have been raised about the long-term safety of the consumption of certain sweeteners(2–5). 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. Nature Publishing Group UK 2023-03-15 2023 /pmc/articles/PMC10033444/ /pubmed/36922598 http://dx.doi.org/10.1038/s41586-023-05801-6 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
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.
The dietary sweetener sucralose is a negative modulator of T cell-mediated responses
title The dietary sweetener sucralose is a negative modulator of T cell-mediated responses
title_full The dietary sweetener sucralose is a negative modulator of T cell-mediated responses
title_fullStr The dietary sweetener sucralose is a negative modulator of T cell-mediated responses
title_full_unstemmed The dietary sweetener sucralose is a negative modulator of T cell-mediated responses
title_short The dietary sweetener sucralose is a negative modulator of T cell-mediated responses
title_sort dietary sweetener sucralose is a negative modulator of t cell-mediated responses
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10033444/
https://www.ncbi.nlm.nih.gov/pubmed/36922598
http://dx.doi.org/10.1038/s41586-023-05801-6
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