Epigenomic variability is associated with age-specific naïve CD4 T cell response to activation in infants and adolescents.
Samira ImranMelanie R NeelandDavid J MartinoStephen PengJennifer KoplinShyamali C DharmageMimi Lk TangSusan SawyerThanh DangVicki McWilliamRachel L PetersSusan PrescottKirsten P PerrettBoris NovakovicRichard SafferyPublished in: Immunology and cell biology (2023)
Childhood is a critical period of immune development. During this time, naïve CD4 (nCD4) T cells undergo programmed cell differentiation, mediated by epigenetic changes, in response to external stimuli leading to a baseline homeostatic state that may determine lifelong disease risk. However, the ontogeny of epigenetic signatures associated with CD4 T cell activation during key developmental periods are yet to be described. We investigated genome-wide DNA methylation (DNAm) changes associated with nCD4 T activation following 72 h culture in media+anti-CD3/CD28 beads in healthy infants (aged 12 months, n = 18) and adolescents (aged 10-15 years, n = 15). We integrated these data with transcriptomic and cytokine profiling from the same samples. nCD4 T cells from both age groups show similar extensive epigenetic reprogramming following activation, with the majority of genes involved in the T cell receptor signaling pathway associated with differential methylation. Additionally, we identified differentially methylated probes showing age-specific responses, that is, responses in only infants or adolescents, including within a cluster of T cell receptor (TCR) genes. These encoded several TCR alpha joining (TRAJ), and TCR alpha variable (TRAV) genes. Cytokine data analysis following stimulation revealed enhanced release of IFN-γ, IL-2 and IL-10, in nCD4 T cells from adolescents compared with infants. Overlapping differential methylation and cytokine responses identified four probes potentially underpinning these age-specific responses. We show that DNAm in nCD4T cells in response to activation is dynamic in infancy and adolescence, with additional evidence for age-specific effects potentially driving variation in cytokine responses between these ages.
Keyphrases
- dna methylation
- genome wide
- young adults
- gene expression
- data analysis
- physical activity
- signaling pathway
- regulatory t cells
- small molecule
- copy number
- depressive symptoms
- immune response
- single molecule
- living cells
- weight gain
- transcription factor
- body mass index
- dna damage
- binding protein
- atomic force microscopy
- endoplasmic reticulum stress
- early life
- weight loss
- fluorescent probe
- induced apoptosis
- mass spectrometry
- genome wide identification