Raw Cow’s Milk Reduces Allergic Symptoms in a Murine Model for Food Allergy—A Potential Role for Epigenetic Modifications
Suzanne Abbring,
Johanna Wolf,
Veronica Ayechu-Muruzabal,
Mara A.P. Diks,
Bilal Alashkar Alhamwe,
Fahd Alhamdan,
Hani Harb,
Harald Renz,
Holger Garn,
Johan Garssen,
Daniel P. Potaczek,
Betty C.A.M. van Esch
Affiliations
Suzanne Abbring
Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, 3584 CG Utrecht, The Netherlands
Johanna Wolf
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
Veronica Ayechu-Muruzabal
Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, 3584 CG Utrecht, The Netherlands
Mara A.P. Diks
Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, 3584 CG Utrecht, The Netherlands
Bilal Alashkar Alhamwe
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
Fahd Alhamdan
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
Hani Harb
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
Harald Renz
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
Holger Garn
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
Johan Garssen
Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, 3584 CG Utrecht, The Netherlands
Daniel P. Potaczek
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
Betty C.A.M. van Esch
Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, 3584 CG Utrecht, The Netherlands
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.