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Epigenetic dysregulation of naive CD4+ T-cell activation genes in childhood food allergy

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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 Saffery
Food 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 communications

Volume

9

Article number

3308

Pagination

1 - 12

Publisher

Nature Publishing Group

Location

London, Eng.

eISSN

2041-1723

Language

eng

Publication classification

C1 Refereed article in a scholarly journal

Copyright notice

2018, The Authors