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

Martino, David, Neeland, Melanie, Dang, Thanh, Cobb, Joanna, Ellis, Justine, Barnett, Alice, Tang, Mimi, Vuillermin, Peter, Allen, Katrina and Saffery, Richard 2018, Epigenetic dysregulation of naive CD4+ T-cell activation genes in childhood food allergy, Nature communications, vol. 9, pp. 1-12, doi: 10.1038/s41467-018-05608-4.

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Title Epigenetic dysregulation of naive CD4+ T-cell activation genes in childhood food allergy
Author(s) Martino, David
Neeland, Melanie
Dang, Thanh
Cobb, Joanna
Ellis, Justine
Barnett, Alice
Tang, Mimi
Vuillermin, Peter
Allen, Katrina
Saffery, Richard
Journal name Nature communications
Volume number 9
Article ID 3308
Start page 1
End page 12
Total pages 12
Publisher Nature Publishing Group
Place of publication London, Eng.
Publication date 2018-08-17
ISSN 2041-1723
Keyword(s) food allergy
childhood
CD4+ T-cell activation
health
infants
T cell receptor
lymphoproliferative response
immunoglobulin E (IgE)
metabolic
inflammatory genes
epigenetic disruption
science & technology
Summary 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.
Language eng
DOI 10.1038/s41467-018-05608-4
Field of Research MD Multidisciplinary
HERDC Research category C1 Refereed article in a scholarly journal
Copyright notice ©2018, The Authors
Free to Read? Yes
Use Rights Creative Commons Attribution licence
Persistent URL http://hdl.handle.net/10536/DRO/DU:30113385

Document type: Journal Article
Collections: School of Medicine
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Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.