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

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 i...

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Main Authors: Bilal Alashkar Alhamwe, Laura A. P. M. Meulenbroek, Désirée H. Veening-Griffioen, Tjalling M. D. Wehkamp, Fahd Alhamdan, Sarah Miethe, Hani Harb, Astrid Hogenkamp, Léon M. J. Knippels, Elke Pogge von Strandmann, Harald Renz, Johan Garssen, Betty C. A. M. van Esch, Holger Garn, Daniel P. Potaczek, Machteld M. Tiemessen
Format: Article
Language:English
Published: MDPI AG 2020-10-01
Series:Nutrients
Subjects:
Online Access:https://www.mdpi.com/2072-6643/12/10/3193
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author Bilal Alashkar Alhamwe
Laura A. P. M. Meulenbroek
Désirée H. Veening-Griffioen
Tjalling M. D. Wehkamp
Fahd Alhamdan
Sarah Miethe
Hani Harb
Astrid Hogenkamp
Léon M. J. Knippels
Elke Pogge von Strandmann
Harald Renz
Johan Garssen
Betty C. A. M. van Esch
Holger Garn
Daniel P. Potaczek
Machteld M. Tiemessen
author_facet Bilal Alashkar Alhamwe
Laura A. P. M. Meulenbroek
Désirée H. Veening-Griffioen
Tjalling M. D. Wehkamp
Fahd Alhamdan
Sarah Miethe
Hani Harb
Astrid Hogenkamp
Léon M. J. Knippels
Elke Pogge von Strandmann
Harald Renz
Johan Garssen
Betty C. A. M. van Esch
Holger Garn
Daniel P. Potaczek
Machteld M. Tiemessen
author_sort Bilal Alashkar Alhamwe
collection DOAJ
description 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 (<i>Stat6</i>) 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.
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spelling doaj.art-aab0e6eca7c94518a9ae8f2e07d217a02023-11-20T17:38:48ZengMDPI AGNutrients2072-66432020-10-011210319310.3390/nu12103193Decreased Histone Acetylation Levels at Th1 and Regulatory Loci after Induction of Food AllergyBilal Alashkar Alhamwe0Laura A. P. M. Meulenbroek1Désirée H. Veening-Griffioen2Tjalling M. D. Wehkamp3Fahd Alhamdan4Sarah Miethe5Hani Harb6Astrid Hogenkamp7Léon M. J. Knippels8Elke Pogge von Strandmann9Harald Renz10Johan Garssen11Betty C. A. M. van Esch12Holger Garn13Daniel P. Potaczek14Machteld M. Tiemessen15Institute 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, GermanyDanone Nutricia Research, 3584 CT Utrecht, The NetherlandsDanone Nutricia Research, 3584 CT Utrecht, The NetherlandsDanone Nutricia Research, 3584 CT Utrecht, The NetherlandsInstitute 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, GermanyInstitute 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, GermanyInstitute 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, GermanyDivision of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, 3584 CT Utrecht, The NetherlandsDanone Nutricia Research, 3584 CT Utrecht, The NetherlandsInstitute of Tumor Immunology, Clinic for Hematology, Oncology and Immunology, Center for Tumor Biology and Immunology, Philipps University Marburg, 35039 Marburg, GermanyInstitute 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, GermanyDanone Nutricia Research, 3584 CT Utrecht, The NetherlandsDanone Nutricia Research, 3584 CT Utrecht, The NetherlandsInstitute 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, GermanyInstitute 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, GermanyDanone Nutricia Research, 3584 CT Utrecht, The NetherlandsImmunoglobulin 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 (<i>Stat6</i>) 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.https://www.mdpi.com/2072-6643/12/10/3193cow’s milk allergyepigeneticsfood allergyhistone acetylationwhey
spellingShingle Bilal Alashkar Alhamwe
Laura A. P. M. Meulenbroek
Désirée H. Veening-Griffioen
Tjalling M. D. Wehkamp
Fahd Alhamdan
Sarah Miethe
Hani Harb
Astrid Hogenkamp
Léon M. J. Knippels
Elke Pogge von Strandmann
Harald Renz
Johan Garssen
Betty C. A. M. van Esch
Holger Garn
Daniel P. Potaczek
Machteld M. Tiemessen
Decreased Histone Acetylation Levels at Th1 and Regulatory Loci after Induction of Food Allergy
Nutrients
cow’s milk allergy
epigenetics
food allergy
histone acetylation
whey
title Decreased Histone Acetylation Levels at Th1 and Regulatory Loci after Induction of Food Allergy
title_full Decreased Histone Acetylation Levels at Th1 and Regulatory Loci after Induction of Food Allergy
title_fullStr Decreased Histone Acetylation Levels at Th1 and Regulatory Loci after Induction of Food Allergy
title_full_unstemmed Decreased Histone Acetylation Levels at Th1 and Regulatory Loci after Induction of Food Allergy
title_short Decreased Histone Acetylation Levels at Th1 and Regulatory Loci after Induction of Food Allergy
title_sort decreased histone acetylation levels at th1 and regulatory loci after induction of food allergy
topic cow’s milk allergy
epigenetics
food allergy
histone acetylation
whey
url https://www.mdpi.com/2072-6643/12/10/3193
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