PMID- 30120223
OWN - NLM
STAT- MEDLINE
DCOM- 20181217
LR  - 20200309
IS  - 2041-1723 (Electronic)
IS  - 2041-1723 (Linking)
VI  - 9
IP  - 1
DP  - 2018 Aug 17
TI  - Epigenetic dysregulation of naive CD4+ T-cell activation genes in childhood food 
      allergy.
PG  - 3308
LID - 10.1038/s41467-018-05608-4 [doi]
LID - 3308
AB  - 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.
FAU - Martino, David
AU  - Martino D
AUID- ORCID: 0000-0001-6823-4696
AD  - Department of Paediatrics, Murdoch Children's Research Institute, The University 
      of Melbourne, Flemington Road, Parkville, VIC, 3052, Australia.
AD  - Telethon Kids Institute, 100 Roberts Road, Perth, WA, Australia.
FAU - Neeland, Melanie
AU  - Neeland M
AD  - Department of Paediatrics, Murdoch Children's Research Institute, The University 
      of Melbourne, Flemington Road, Parkville, VIC, 3052, Australia.
FAU - Dang, Thanh
AU  - Dang T
AD  - Department of Paediatrics, Murdoch Children's Research Institute, The University 
      of Melbourne, Flemington Road, Parkville, VIC, 3052, Australia.
FAU - Cobb, Joanna
AU  - Cobb J
AD  - Department of Paediatrics, Murdoch Children's Research Institute, The University 
      of Melbourne, Flemington Road, Parkville, VIC, 3052, Australia.
FAU - Ellis, Justine
AU  - Ellis J
AD  - Department of Paediatrics, Murdoch Children's Research Institute, The University 
      of Melbourne, Flemington Road, Parkville, VIC, 3052, Australia.
FAU - Barnett, Alice
AU  - Barnett A
AD  - Department of Paediatrics, Murdoch Children's Research Institute, The University 
      of Melbourne, Flemington Road, Parkville, VIC, 3052, Australia.
FAU - Tang, Mimi
AU  - Tang M
AD  - Department of Paediatrics, Murdoch Children's Research Institute, The University 
      of Melbourne, Flemington Road, Parkville, VIC, 3052, Australia.
FAU - Vuillermin, Peter
AU  - Vuillermin P
AD  - Department of Paediatrics, Murdoch Children's Research Institute, The University 
      of Melbourne, Flemington Road, Parkville, VIC, 3052, Australia.
AD  - Barwon Health, Geelong, VIC, 3220, Australia.
AD  - Deakin University, Geelong, VIC, 3216, Australia.
FAU - Allen, Katrina
AU  - Allen K
AD  - Department of Paediatrics, Murdoch Children's Research Institute, The University 
      of Melbourne, Flemington Road, Parkville, VIC, 3052, Australia. 
      katrina.allen@mcri.edu.au.
FAU - Saffery, Richard
AU  - Saffery R
AUID- ORCID: 0000-0002-9510-4181
AD  - Department of Paediatrics, Murdoch Children's Research Institute, The University 
      of Melbourne, Flemington Road, Parkville, VIC, 3052, Australia.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180817
PL  - England
TA  - Nat Commun
JT  - Nature communications
JID - 101528555
SB  - IM
MH  - CD4-Positive T-Lymphocytes/*immunology
MH  - Case-Control Studies
MH  - Child
MH  - Child, Preschool
MH  - Cluster Analysis
MH  - DNA Methylation/genetics
MH  - *Epigenesis, Genetic
MH  - Food Hypersensitivity/*genetics/*immunology
MH  - Gene Expression Profiling
MH  - Humans
MH  - Infant
MH  - Lymphocyte Activation/*genetics
MH  - Polymorphism, Genetic
PMC - PMC6098117
COIS- The authors declare no competing interests.
EDAT- 2018/08/19 06:00
MHDA- 2018/12/18 06:00
PMCR- 2018/08/17
CRDT- 2018/08/19 06:00
PHST- 2017/11/30 00:00 [received]
PHST- 2018/06/05 00:00 [accepted]
PHST- 2018/08/19 06:00 [entrez]
PHST- 2018/08/19 06:00 [pubmed]
PHST- 2018/12/18 06:00 [medline]
PHST- 2018/08/17 00:00 [pmc-release]
AID - 10.1038/s41467-018-05608-4 [pii]
AID - 5608 [pii]
AID - 10.1038/s41467-018-05608-4 [doi]
PST - epublish
SO  - Nat Commun. 2018 Aug 17;9(1):3308. doi: 10.1038/s41467-018-05608-4.