Epigenetic dysregulation of naive CD4+ T-cell activation genes in childhood food allergy.
David J MartinoMelanie NeelandThanh DangJoanna CobbJustine EllisAlice BarnettMimi TangPeter VuillerminKatrina AllenRichard SafferyPublished in: Nature communications (2018)
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.
Keyphrases
- dna methylation
- genome wide
- transcription factor
- cell cycle
- genome wide identification
- gene expression
- public health
- copy number
- epstein barr virus
- young adults
- cell proliferation
- oxidative stress
- hiv infected
- single cell
- signaling pathway
- poor prognosis
- binding protein
- genome wide analysis
- electronic health record
- pi k akt
- bioinformatics analysis
- dna binding
- big data
- early life
- childhood cancer
- artificial intelligence
- deep learning
- long non coding rna
- data analysis