vuillermin-epigeneticdysregulation-2018.pdf (1.57 MB)
Epigenetic dysregulation of naive CD4+ T-cell activation genes in childhood food allergy
journal contribution
posted on 2018-08-17, 00:00 authored by David Martino, Melanie Neeland, Thanh Dang, Joanna Cobb, Justine Ellis, Alice Barnett, Mimi Tang, Peter VuillerminPeter Vuillermin, Katrina Allen, Richard SafferyFood allergy poses a significant clinical and public health burden affecting 2-10% of infants. Using integrated DNA methylation and transcriptomic profiling, we found that polyclonal activation of naive CD4+ T cells through the T cell receptor results in poorer lymphoproliferative responses in children with immunoglobulin E (IgE)-mediated food allergy. Reduced expression of cell cycle-related targets of the E2F and MYC transcription factor networks, and remodeling of DNA methylation at metabolic (RPTOR, PIK3D, MAPK1, FOXO1) and inflammatory genes (IL1R, IL18RAP, CD82) underpins this suboptimal response. Infants who fail to resolve food allergy in later childhood exhibit cumulative increases in epigenetic disruption at T cell activation genes and poorer lymphoproliferative responses compared to children who resolved food allergy. Our data indicate epigenetic dysregulation in the early stages of signal transduction through the T cell receptor complex, and likely reflects pathways modified by gene-environment interactions in food allergy.
History
Journal
Nature communicationsVolume
9Article number
3308Pagination
1 - 12Publisher
Nature Publishing GroupLocation
London, Eng.Publisher DOI
Link to full text
eISSN
2041-1723Language
engPublication classification
C1 Refereed article in a scholarly journalCopyright notice
2018, The AuthorsUsage metrics
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food allergychildhoodCD4+ T-cell activationhealthinfantsT cell receptorlymphoproliferative responseimmunoglobulin E (IgE)metabolicinflammatory genesepigenetic disruptionScience & TechnologyMultidisciplinary SciencesScience & Technology - Other TopicsT-CELLCHILDRENIDENTIFICATIONASSOCIATIONMATURATIONRESPONSESBINDING
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