TY - JOUR
T1 - Decreased Histone Acetylation Levels at Th1 and Regulatory Loci after Induction of Food Allergy
AU - Alashkar Alhamwe, Bilal
AU - Meulenbroek, Laura A P M
AU - Veening-Griffioen, Désirée H
AU - Wehkamp, Tjalling M D
AU - Alhamdan, Fahd
AU - Miethe, Sarah
AU - Harb, Hani
AU - Hogenkamp, Astrid
AU - Knippels, Léon M J
AU - Pogge von Strandmann, Elke
AU - Renz, Harald
AU - Garssen, Johan
AU - van Esch, Betty C A M
AU - Garn, Holger
AU - Potaczek, Daniel P
AU - Tiemessen, Machteld M
PY - 2020/10/19
Y1 - 2020/10/19
N2 - 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.
AB - 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.
KW - cow’s milk allergy
KW - epigenetics
KW - food allergy
KW - histone acetylation
KW - whey
U2 - 10.3390/nu12103193
DO - 10.3390/nu12103193
M3 - Article
C2 - 33086571
SN - 2072-6643
VL - 12
JO - Nutrients
JF - Nutrients
IS - 10
M1 - 3193
ER -