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.