Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, 3584 CG Utrecht, The Netherlands.
Institute of Laboratory Medicine, Member of the German Center for Lung Research (DZL) and the Universities of Giessen and Marburg Lung Center (UGMLC), 35043 Marburg, Germany.
Nutrients. 2019 Jul 25;11(8):1721. doi: 10.3390/nu11081721.
Epidemiological studies identified raw cow's milk consumption as an important environmental exposure that prevents allergic diseases. In the present study, we investigated whether raw cow's milk has the capacity to induce tolerance to an unrelated, non-milk, food allergen. Histone acetylation of T cell genes was investigated to assess potential epigenetic regulation. Female C3H/HeOuJ mice were sensitized and challenged to ovalbumin. Prior to sensitization, the mice were treated with raw milk, processed milk, or phosphate-buffered saline for eight days. Allergic symptoms were assessed after challenge and histone modifications in T cell-related genes of splenocyte-derived CD4 T cells and the mesenteric lymph nodes were analyzed after milk exposure and after challenge. Unlike processed milk, raw milk decreased allergic symptoms. After raw milk exposure, histone acetylation of Th1-, Th2-, and regulatory T cell-related genes of splenocyte-derived CD4 T cells was higher than after processed milk exposure. After allergy induction, this general immune stimulation was resolved and histone acetylation of Th2 genes was lower when compared to processed milk. Raw milk reduces allergic symptoms to an unrelated, non-milk, food allergen in a murine model for food allergy. The activation of T cell-related genes could be responsible for the observed tolerance induction, which suggested that epigenetic modifications contribute to the allergy-protective effect of raw milk.
流行病学研究表明，食用生牛乳是预防过敏疾病的重要环境暴露因素。本研究旨在探讨生牛乳是否具有诱导对非相关的、非乳类食物过敏原产生耐受的能力。通过检测 T 细胞基因的组蛋白乙酰化来评估潜在的表观遗传调控。雌性 C3H/HeOuJ 小鼠经卵清蛋白致敏和激发后，用生牛乳、处理牛乳或磷酸盐缓冲液处理 8 天。激发后评估过敏症状，并分析致敏前和激发后乳暴露及激发后，来源于脾 CD4 T 细胞和肠系膜淋巴结的 T 细胞相关基因的组蛋白修饰。与处理牛乳不同，生牛乳可降低过敏症状。生牛乳暴露后，来源于脾 CD4 T 细胞的 Th1、Th2 和调节性 T 细胞相关基因的组蛋白乙酰化水平高于处理牛乳。过敏诱导后，与处理牛乳相比，这种普遍的免疫刺激得到缓解，Th2 基因的组蛋白乙酰化水平降低。生牛乳可降低食物过敏小鼠模型中非相关的、非乳类食物过敏原的过敏症状。T 细胞相关基因的激活可能是观察到的耐受诱导的原因，这表明表观遗传修饰有助于生牛乳的抗过敏作用。
