Mechanisms linking ingested pollutants to increased incidence of allergy are poorly understood. We report that mice exposed to low doses of cadmium develop higher IgE responses following oral allergen sensitization and more severe allergic symptoms upon allergen challenge. The environmentally relevant doses of this pollutant also induced oxidative/inflammatory responses in the gut of SPF, but not germ-free mice. Interestingly, the increased IgE responses correlated with stimulation of the vitamin D₃-metabolizing enzymes CYP27B1 and CYP24A1 in the gut and increased luminal levels of oxidized vitamin D₃ metabolites that are not ligands of the vitamin D receptor. Inhibition of CYP27B1 and CYP24A1 via oral administration of pharmacological inhibitors reduced IgE responses induced in mice orally exposed to cadmium. Our findings identify local alteration of vitamin D signaling as a new mechanism for induction of IgE responses by environmental pollutants. They also identify vitamin D3-metabolizing enzymes as therapeutic targets for the treatment of allergy.

人们对摄入污染物与过敏发生率增加之间的联系机制知之甚少。我们报告说，暴露于低剂量镉的小鼠在口服过敏原致敏后产生更高的 IgE 反应，并在过敏原激发后产生更严重的过敏症状。这种污染物的环境相关剂量也会诱导 SPF 肠道内的氧化/炎症反应，但无菌小鼠则不会。有趣的是，IgE 反应的增加与肠道中维生素 D ₃代谢酶 CYP27B1 和 CYP24A1 的刺激以及非维生素 D 受体配体的氧化维生素 D _{3代谢物的管腔水平增加相关。}通过口服药物抑制剂抑制 CYP27B1 和 CYP24A1，可降低口服镉小鼠中诱导的 IgE 反应。我们的研究结果表明，维生素 D 信号的局部改变是环境污染物诱导 IgE 反应的新机制。他们还将维生素 D3 代谢酶确定为治疗过敏的治疗靶点。