A Western diet (WD)—characterized by its high fat and simple sugar content—is thought to predispose individuals to inflammatory skin diseases such as psoriasis through the development of obesity. This scenario, however, is being challenged by emerging data suggesting that dietary components, rather than obesity itself, may exacerbate psoriasis. We herein show that short-term feeding with a diet analogous to the WD in mice leads to T helper type 1–/T helper type 17–biased skin inflammation before significant body weight gain. Feeding for as little as 4 weeks with a WD promoted mild dermatitis and accumulation of IL-17A–producing γδ T cells in the skin. Strikingly, γδ T cells from WD-fed mice exhibited enriched IL-23 receptor expression and increased the potential to produce IL-17A after IL-23 stimulation. In contrast to wild-type mice, WD-fed TCRδ–deficient and CCR6-deficient mice had reduced skin inflammation and IL-17A expression. Supplementation with a bile acid sequestrant, cholestyramine, prevented WD-induced skin inflammation along with a reduction in the infiltration of γδ T cells and the expression of proinflammatory mediators. In summary, our data revealed dietary influences in inflammatory signaling in the skin. The dysregulation of IL-23 pathways and bile acid pathways may be key to the development of WD-associated psoriasiform dermatitis.

西方饮食 (WD) 以高脂肪和单糖含量为特征，被认为会通过肥胖的发展使个体易患炎症性皮肤病，例如牛皮癣。然而，这种情况正受到新数据的挑战，这些数据表明饮食成分而不是肥胖本身可能会加剧银屑病。我们在此表明​​，在小鼠体重显着增加之前，短期喂食类似于 WD 的饮食会导致 T 辅助 1 型/T 辅助 17 型偏向性皮肤炎症。喂食 WD 仅 4 周会促进轻度皮炎和皮肤中产生 IL-17A 的 γδ T 细胞的积累。引人注目的是，来自 WD 喂养小鼠的 γδ T 细胞表现出丰富的 IL-23 受体表达，并增加了在 IL-23 刺激后产生 IL-17A 的潜力。与野生型小鼠相比，WD 喂养的 TCRδ 缺陷和 CCR6 缺陷小鼠的皮肤炎症和 IL-17A 表达减少。补充胆汁酸螯合剂消胆胺可预防 WD 诱导的皮肤炎症，同时减少 γδ T 细胞的浸润和促炎介质的表达。总之，我们的数据揭示了饮食对皮肤炎症信号的影响。IL-23 通路和胆汁酸通路的失调可能是 WD 相关银屑病样皮炎发展的关键。我们的数据揭示了饮食对皮肤炎症信号的影响。IL-23 通路和胆汁酸通路的失调可能是 WD 相关银屑病样皮炎发展的关键。我们的数据揭示了饮食对皮肤炎症信号的影响。IL-23 通路和胆汁酸通路的失调可能是 WD 相关银屑病样皮炎发展的关键。