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). 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.

Automated summary

Artificial sweeteners, calorie-free substitutes for sugar, are widely used in many food products. However, concerns have been raised about the long-term safety of consuming certain sweeteners. This study shows that high doses of sucralose can have immunomodulatory effects, limiting T cell proliferation and differentiation, affecting membrane order, T cell receptor signaling, and intracellular calcium mobilization. Mice given sucralose showed decreased T cell responses in cancer and bacterial infection models, as well as reduced T cell function in autoimmune models. These findings suggest that sucralose intake can dampen T cell-mediated responses, which may be useful in treating T cell-dependent autoimmune disorders.