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

Autor:	Alashkar Alhamwe B; 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.; College of Pharmacy, International University for Science and Technology (IUST), Daraa 15, Syria., Meulenbroek LAPM; 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., Veening-Griffioen DH; 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., Wehkamp TMD; 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., Alhamdan F; 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.; Translational Inflammation Research Division & Core Facility for Single Cell Multiomics, the German Center for Lung Research (DZL), Universities of Giessen and Marburg Lung Center, Philipps University Marburg, 35039 Marburg, Germany., Miethe S; 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.; Translational Inflammation Research Division & Core Facility for Single Cell Multiomics, the German Center for Lung Research (DZL), Universities of Giessen and Marburg Lung Center, Philipps University Marburg, 35039 Marburg, Germany., Harb H; 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.; Division of Immunology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA., Hogenkamp A; Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, 3584 CT Utrecht, The Netherlands., Knippels LMJ; 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., Pogge von Strandmann E; Institute of Tumor Immunology, Clinic for Hematology, Oncology and Immunology, Center for Tumor Biology and Immunology, Philipps University Marburg, 35039 Marburg, Germany., Renz H; 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., Garssen J; 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., van Esch BCAM; 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., Garn H; 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.; Translational Inflammation Research Division & Core Facility for Single Cell Multiomics, the German Center for Lung Research (DZL), Universities of Giessen and Marburg Lung Center, Philipps University Marburg, 35039 Marburg, Germany., Potaczek DP; 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.; Translational Inflammation Research Division & Core Facility for Single Cell Multiomics, the German Center for Lung Research (DZL), Universities of Giessen and Marburg Lung Center, Philipps University Marburg, 35039 Marburg, Germany.; John Paul II Hospital, 31-202 Krakow, Poland., Tiemessen MM; 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.
Jazyk:	angličtina
Zdroj:	Nutrients [Nutrients] 2020 Oct 19; Vol. 12 (10). Date of Electronic Publication: 2020 Oct 19.
DOI:	10.3390/nu12103193
Abstrakt:	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. Competing Interests: L.M., D.H.V.-G., T.M.D.W., L.M.J.K., J.G., B.C.A.M.v.E., and M.M.T. are/were (partly) employed at Danone Nutricia Research. D.H.V.-G reports personal fees from Merck Sharp & Dohme outside of the submitted work. All other authors report no potential conflict of interest.
Databáze:	MEDLINE
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