Abstract
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.
Highlights
Food allergy poses a significant clinical and public health burden affecting 2–10% of infants
We explored whether T cell activation-induced changes in the epigenetic and transcriptional landscape were related to food allergy status in samples collected at baseline (12-month infants)
We found evidence for six associations (FDR P value
Summary
Food allergy poses a significant clinical and public health burden affecting 2–10% of infants. Attenuated T cell signaling[11] and regulatory T cell (Treg)-suppressive function[12] have been reported among neonates that acquire food allergies in infancy These initiating mechanisms reflect the early dysregulation of immune development and likely predispose to the eventual failure of mucosal networks that mediate oral tolerance. We have previously described differences in neonatal total CD4+ T cell activation gene response capacity and proliferative potential in children who eventually develop food allergy in the first year of life[11] These differences are apparent at birth at an age that is unrelated to allergen exposure and of unknown clinical significance. Our data reveal a molecular pattern of T cell activation gene dysregulation in infants with food allergy, associated with poor lymphoproliferative responses
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
