TY - JOUR
T1 - The dietary sweetener sucralose is a negative modulator of T cell-mediated responses
AU - Zani, Fabio
AU - Blagih, Julianna
AU - Gruber, Tim
AU - Buck, Michael D.
AU - Jones, Nicholas
AU - Hennequart, Marc
AU - Newell, Clare L.
AU - Pilley, Steven E.
AU - Soro-Barrio, Pablo
AU - Kelly, Gavin
AU - Legrave, Nathalie M.
AU - Cheung, Eric C.
AU - Gilmore, Ian S.
AU - Gould, Alex P.
AU - Garcia-Caceres, Cristina
AU - Vousden, Karen H.
N1 - Publisher Copyright:
© 2023, The Author(s).
PY - 2023/3/23
Y1 - 2023/3/23
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85149970802&partnerID=8YFLogxK
UR - https://pubmed.ncbi.nlm.nih.gov/36922598
U2 - 10.1038/s41586-023-05801-6
DO - 10.1038/s41586-023-05801-6
M3 - Article
C2 - 36922598
AN - SCOPUS:85149970802
SN - 0028-0836
VL - 615
SP - 705
EP - 711
JO - Nature
JF - Nature
IS - 7953
ER -