@article{b187ccf2388042acb876f6a48a4fc4bb,
title = "The dietary sweetener sucralose is a negative modulator of T cell-mediated responses",
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.",
author = "Fabio Zani and Julianna Blagih and Tim Gruber and Buck, {Michael D.} and Nicholas Jones and Marc Hennequart and Newell, {Clare L.} and Pilley, {Steven E.} and Pablo Soro-Barrio and Gavin Kelly and Legrave, {Nathalie M.} and Cheung, {Eric C.} and Gilmore, {Ian S.} and Gould, {Alex P.} and Cristina Garcia-Caceres and Vousden, {Karen H.}",
note = "Funding Information: The authors thank R. Goldstone and D. Jackson for help with the RNA-seq experiment; A. Horwood, C. Zverev, S. Lighterness, C. Lathlean and the Crick BRF for the help with animal experiments; the Crick flow cytometry facility for help with sorting and flow cytometry experiments; C. Charoy and the Crick Light Microscopy Facility; the Vinuesa laboratory for sharing their sheep red blood cell immunization protocol; Y. Lee for input on immunoprecipitation. This work was funded by Cancer Research UK grant C596/A26855 and supported by the Francis Crick Institute which receives its core funding from Cancer Research UK (CC2073, CC2101, CC1067 and CC1107), the UK Medical Research Council (CC2073, CC2101, CC1067 and CC1107) and the Wellcome Trust (CC2073, CC2101, CC1067 and CC1107). M.D.B. is funded by the EMBO Long-Term Fellowship ALTF 1096-2018 and Marie Sk{\l}odowska-Curie Individual Fellowship 837951. J.B. is funded by the Kuok Family Fellowship. N.J. is funded by an MRC New Investigator Research Grant (MR/X000095/1). C.L.N., I.S.G. and A.P.G. are supported by funding from the Wellcome Trust (223760/Z/14/Z). C.G.-C. is funded by the European Research Council ERC (STG grant AstroNeuroCrosstalk no. 757393), the German Research Foundation DFG under Germany{\textquoteright}s Excellence Strategy within the framework of the Munich Cluster for Systems Neurology (EXC 2145 SyNergy, ID 390857198) and Helmholtz Excellence Network and the Deutsche Forschungsgemeinschaft (GS: SPP1757–SA2114/2-2), and Helmholtz Association—Initiative and Networking Fund. This work forms part of the 3D OrbiSIMS project in the Life Science and Health programme of the National Measurement System of the UK Department of Business, Energy and Industrial strategy. Funding Information: The authors thank R. Goldstone and D. Jackson for help with the RNA-seq experiment; A. Horwood, C. Zverev, S. Lighterness, C. Lathlean and the Crick BRF for the help with animal experiments; the Crick flow cytometry facility for help with sorting and flow cytometry experiments; C. Charoy and the Crick Light Microscopy Facility; the Vinuesa laboratory for sharing their sheep red blood cell immunization protocol; Y. Lee for input on immunoprecipitation. This work was funded by Cancer Research UK grant C596/A26855 and supported by the Francis Crick Institute which receives its core funding from Cancer Research UK (CC2073, CC2101, CC1067 and CC1107), the UK Medical Research Council (CC2073, CC2101, CC1067 and CC1107) and the Wellcome Trust (CC2073, CC2101, CC1067 and CC1107). M.D.B. is funded by the EMBO Long-Term Fellowship ALTF 1096-2018 and Marie Sk{\l}odowska-Curie Individual Fellowship 837951. J.B. is funded by the Kuok Family Fellowship. N.J. is funded by an MRC New Investigator Research Grant (MR/X000095/1). C.L.N., I.S.G. and A.P.G. are supported by funding from the Wellcome Trust (223760/Z/14/Z). C.G.-C. is funded by the European Research Council ERC (STG grant AstroNeuroCrosstalk no. 757393), the German Research Foundation DFG under Germany{\textquoteright}s Excellence Strategy within the framework of the Munich Cluster for Systems Neurology (EXC 2145 SyNergy, ID 390857198) and Helmholtz Excellence Network and the Deutsche Forschungsgemeinschaft (GS: SPP1757–SA2114/2-2), and Helmholtz Association—Initiative and Networking Fund. This work forms part of the 3D OrbiSIMS project in the Life Science and Health programme of the National Measurement System of the UK Department of Business, Energy and Industrial strategy. Funding Information: K.H.V. is on the board of directors and shareholder of Bristol Myers Squibb and on the scientific advisory board (with stock options) of PMV Pharma, RAZE Therapeutics, Volastra Pharmaceuticals and Kovina Therapeutics. She is on the scientific advisory board of Ludwig Cancer and a co-founder and consultant of Faeth Therapeutics. She has been in receipt of research funding from Astex Pharmaceuticals and AstraZeneca and contributed to CRUK Cancer Research Technology filing of patent application WO/2017/144877. J.B. is funded by a fellowship from the Kuok Family, who did not influence any aspects of the research. The other authors declare no competing interests. Publisher Copyright: {\textcopyright} 2023, The Author(s).",
year = "2023",
month = mar,
day = "23",
doi = "10.1038/s41586-023-05801-6",
language = "English",
volume = "615",
pages = "705--711",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Research",
number = "7953",
}
