Decreased Histone Acetylation Levels at Th1 and Regulatory Loci after Induction of Food Allergy

Nutrients

Désirée H. Veening-Griffioen¹  Tjalling M.D. Wehkamp¹  Betty C.A.M. van Esch¹  Léon M.J. Knippels¹  Laura A.P.M. Meulenbroek¹  Machteld M. Tiemessen¹  Johan Garssen¹  Astrid Hogenkamp²  Holger Garn³  Hani Harb³  Fahd Alhamdan³  Daniel P. Potaczek³  Bilal Alashkar Alhamwe³  Sarah Miethe³  Harald Renz³  Elke Pogge von Strandmann⁴ 

[1] Danone Nutricia Research, 3584 CT Utrecht, The Netherlands;Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, 3584 CT Utrecht, The Netherlands;Institute of Laboratory Medicine, the German Center for Lung Research (DZL) and the Universities of Giessen and Marburg Lung Center (UGMLC), Philipps University Marburg, 35039 Marburg, Germany;Institute of Tumor Immunology, Clinic for Hematology, Oncology and Immunology, Center for Tumor Biology and Immunology, Philipps University Marburg, 35039 Marburg, Germany;

关键词: cow’s milk allergy;    epigenetics;    food allergy;    histone acetylation;    whey;   

DOI  :  10.3390/nu12103193

来源: DOAJ

【 摘 要 】

Immunoglobulin E (IgE)-mediated allergy against cow’s milk protein fractions such as whey is one of the most common food-related allergic disorders of early childhood. Histone acetylation is an important epigenetic mechanism, shown to be involved in the pathogenesis of allergies. However, its role in food allergy remains unknown. IgE-mediated cow’s milk allergy was successfully induced in a mouse model, as demonstrated by acute allergic symptoms, whey-specific IgE in serum, and the activation of mast cells upon a challenge with whey protein. The elicited allergic response coincided with reduced percentages of regulatory T (Treg) and T helper 17 (Th17) cells, matching decreased levels of H3 and/or H4 histone acetylation at pivotal Treg and Th17 loci, an epigenetic status favoring lower gene expression. In addition, histone acetylation levels at the crucial T helper 1 (Th1) loci were decreased, most probably preceding the expected reduction in Th1 cells after inducing an allergic response. No changes were observed for T helper 2 cells. However, increased histone acetylation levels, promoting gene expression, were observed at the signal transducer and activator of transcription 6 (Stat6) gene, a proallergic B cell locus, which was in line with the presence of whey-specific IgE. In conclusion, the observed histone acetylation changes are pathobiologically in line with the successful induction of cow’s milk allergy, to which they might have also contributed mechanistically.

【 授权许可】

Unknown