Epigenetic dysregulation of naive CD4 T-cell activation genes in childhood food allergy
David Martino, Melanie Neeland, Thanh Dang, Joanna Cobb, Justine Ellis, Alice Barnett, Mimi Tang, Peter Vuillermin, Katrina Allen, Richard Saffery
NATURE COMMUNICATIONS | NATURE PUBLISHING GROUP | Published : 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 ..View full abstract
Awarded by National Health and Medical Research Foundation
Awarded by DHB Foundation
We wish to acknowledge the contribution of the HealthNuts investigators Shyamali Dharmage, MBBS, MSc, Melissa Wake, MD, FRACP, Lyle Gurrin, PhD, Anne-Louise Ponsonby, MBBS, FAFPHM, FRACP, PhD, Adrian Lowe, PhD, Terrance Dwyer, PhD, and Melanie Matherson, PhD. We wish to thank the families and study participants involved in the HealthNuts study. Leone Thiele, BA, MNSc, Helen Czech, RN, Jeeva Sanjeevan, MBBS, Marnie Robinson, MBBS, FRACP, Dean Tey, MBBS, FRACP, Hern-Tze Tina Tan, PhD, Deborah Anderson, RN, and Giovanni Zurzolo, BSc, contributed to collection of data through recruitment of infants in immunization sessions and/or food challenges. Belinda Phipson and Jovana Maksimovic provided advice on bioinformatics. This work was supported by the National Health and Medical Research Foundation (GNT1084017), the DHB Foundation (CT21242), and the Victorian Government's Operational Infrastructure program.