Neonatal monocytes exhibit a unique histone modification landscape.

Area of Science:

• Immunology
• Epigenetics
• Neonatal Health

Background:

• Neonates exhibit reduced pro-inflammatory cytokine expression and impaired pathogen clearance, increasing infection susceptibility.
• The regulatory factors governing neonatal immune responses remain poorly understood.
• Epigenetic mechanisms, such as histone modifications, influence gene transcription and immune cell function but are understudied in neonates.

Purpose of the Study:

• To investigate the role of histone modifications in neonatal immune cell function.
• To compare the epigenetic landscape of neonatal and adult immune cells.

Main Methods:

• Chromatin immunoprecipitation (ChIP) performed on mononuclear cells from 45 healthy neonates.
• Chromatin immunoprecipitation with massively parallel DNA sequencing (ChIP-seq) to analyze histone modification landscapes (H3K4me3, H3K9me3, H3K27me3, H3K4me1, H3K27ac, H3K36me3) in neonatal and adult CD14+ monocytes.

Main Results:

• Activating H3K4me3 increased on pro-inflammatory cytokine promoters (IL1B, IL6, IL12B, TNF) as gestation approached term.
• Preterm neonates showed less accessible promoters compared to term neonates, indicated by no change in repressive H3K27me3.
• Monocytes transitioned from a poised enhancer mark (H3K4me1) to an activating mark (H3K4me3) from neonate to adult.
• Decreased H3K4me3 abundance at neonatal monocyte gene promoters (CCR2, CD300C, ILF2, IL1B, TNF) correlated with reduced gene expression.

Conclusions:

• Neonatal immune cells possess a unique epigenetic state distinct from adults.
• This epigenetic state contributes to neonatal-specific immune responses and heightened vulnerability to infections.