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...
Main Authors: | , , , , , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2020-10-01
|
Series: | Nutrients |
Subjects: | |
Online Access: | https://www.mdpi.com/2072-6643/12/10/3193 |
_version_ | 1797550537892167680 |
---|---|
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. |
first_indexed | 2024-03-10T15:30:46Z |
format | Article |
id | doaj.art-aab0e6eca7c94518a9ae8f2e07d217a0 |
institution | Directory Open Access Journal |
issn | 2072-6643 |
language | English |
last_indexed | 2024-03-10T15:30:46Z |
publishDate | 2020-10-01 |
publisher | MDPI AG |
record_format | Article |
series | Nutrients |
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 |
work_keys_str_mv | AT bilalalashkaralhamwe decreasedhistoneacetylationlevelsatth1andregulatorylociafterinductionoffoodallergy AT lauraapmmeulenbroek decreasedhistoneacetylationlevelsatth1andregulatorylociafterinductionoffoodallergy AT desireehveeninggriffioen decreasedhistoneacetylationlevelsatth1andregulatorylociafterinductionoffoodallergy AT tjallingmdwehkamp decreasedhistoneacetylationlevelsatth1andregulatorylociafterinductionoffoodallergy AT fahdalhamdan decreasedhistoneacetylationlevelsatth1andregulatorylociafterinductionoffoodallergy AT sarahmiethe decreasedhistoneacetylationlevelsatth1andregulatorylociafterinductionoffoodallergy AT haniharb decreasedhistoneacetylationlevelsatth1andregulatorylociafterinductionoffoodallergy AT astridhogenkamp decreasedhistoneacetylationlevelsatth1andregulatorylociafterinductionoffoodallergy AT leonmjknippels decreasedhistoneacetylationlevelsatth1andregulatorylociafterinductionoffoodallergy AT elkepoggevonstrandmann decreasedhistoneacetylationlevelsatth1andregulatorylociafterinductionoffoodallergy AT haraldrenz decreasedhistoneacetylationlevelsatth1andregulatorylociafterinductionoffoodallergy AT johangarssen decreasedhistoneacetylationlevelsatth1andregulatorylociafterinductionoffoodallergy AT bettycamvanesch decreasedhistoneacetylationlevelsatth1andregulatorylociafterinductionoffoodallergy AT holgergarn decreasedhistoneacetylationlevelsatth1andregulatorylociafterinductionoffoodallergy AT danielppotaczek decreasedhistoneacetylationlevelsatth1andregulatorylociafterinductionoffoodallergy AT machteldmtiemessen decreasedhistoneacetylationlevelsatth1andregulatorylociafterinductionoffoodallergy |