Sucralose attenuates CD8+ T cell-mediated autoimmunity via IL-20RB upregulation: implications for dietary immunomodulation in vitiligo

Autoimmune diseases are characterized by aberrant immune responses targeting self-tissues, with limited clinical treatment options due to incomplete therapeutic efficacy and drawbacks in safety, accessibility and cost. Dietary factors are known to regulate immune homeostasis, yet the effects of specific common food additives on T cell responses in autoimmune diseases remain largely unclear. Sucralose is a ubiquitous non-nutritive sweetener in daily consumption, and its modulatory role in immune responses has been noticed. This study uses vitiligo, a classic CD8 + T cell-mediated autoimmune disease, to explore the immunomodulatory mechanism of sucralose in autoimmune diseases. This study established a mouse model of vitiligo to evaluate the in vivo effect of oral sucralose administration. We assessed the phenotypic changes of vitiligo lesions, including skin depigmentation, epidermal CD8 + T cell infiltration and melanocyte retention. In vitro experiments were performed using CD8 + T cells isolated from patients with vitiligo and healthy controls to assess the impact of sucralose on the activation and effector function of human CD8 + T cells. Transcriptomic analysis was conducted to screen key sucralose-responsive genes in CD8 + T cells, and gene knockdown and overexpression assays were further used to validate the molecular mechanism underlying sucralose-mediated immune regulation. In vivo , oral sucralose treatment markedly delayed skin depigmentation, reduced epidermal CD8 + T cell infiltration, and protected melanocytes in the vitiligo mouse model. In vitro , sucralose significantly downregulated the expression of the cytotoxic and inflammatory mediators interferon-γ (IFN-γ) and granzyme B, thereby suppressing the effector function of activated CD8 + T cells. Transcriptomic screening identified interleukin-20 receptor subunit beta (IL-20RB) as a significantly upregulated gene induced by sucralose in CD8 + T cells. Functional validation experiments confirmed that IL-20RB is required for the immunosuppressive effects of sucralose. IL-20RB knockdown attenuated sucralose-mediated inhibition of CD8 + T cell activation, while IL-20RB overexpression independently reproduced the immunoregulatory effects of sucralose. This study identifies a novel diet-responsive immune regulatory pathway, in which sucralose restrains CD8 + T cell responses via upregulating IL-20RB expression, thereby alleviating the progression of vitiligo. These exploratory findings suggest that sucralose may modulate T cell-mediated autoimmunity and warrant further investigation under physiologically relevant conditions.