Epigenetic regulation of pediatric and neonatal immune responses

Epigenetic regulation of transcription is a collective term that refers to mechanisms known to regulate gene transcription without changing the underlying DNA sequence. These mechanisms include DNA methylation and histone tail modifications which influence chromatin accessibility, and microRNAs that act through post-transcriptional gene silencing. Epigenetics is known to regulate a variety of biological processes, and the role of epigtenetics in immunity and immune-mediated diseases is becoming increasingly recognized. While DNA methylation is the most widely studied, each of these systems play an important role in the development and maintenance of appropriate immune responses. There is clear evidence that epigenetic mechanisms contribute to developmental stage-specific immune responses in a cell-specific manner. There is also mounting evidence that prenatal exposures alter epigenetic profiles and subsequent immune function in exposed offspring. Early life exposures that are associated with poor long-term health outcomes also appear to impact immune specific epigenetic patterning. Finally, each of these epigenetic mechanisms contribute to the pathogenesis of a wide variety of diseases that manifest during childhood. This review will discuss each of these areas in detail. IMPACT: Epigenetics, including DNA methylation, histone tail modifications, and microRNA expression, dictate immune cell phenotypes. Epigenetics influence immune development and subsequent immune health. Prenatal, perinatal, and postnatal exposures alter immune cell epigenetic profiles and subsequent immune function. Numerous pediatric-onset diseases have an epigenetic component. Several successful strategies for childhood diseases target epigenetic mechanisms.