Fig. 4. Epigenetic reprogramming underlies the induction of trained immunity.

Stimulation of innate immune cells is accompanied by the deposition of chromatin marks and changes in the DNA methylation status, leading to unfolding of chromatin and facilitating transcription and expression of proinflammatory factors. All of these changes are only partially removed after cessation of the stimulus. This allows quicker and enhanced recruitment of transcription factors and gene expression after secondary challenge with another stimulus. The figure illustrates the chromatin states and epigenetic signatures associated with unstimulated cells, with cells following acute stimulation, with resting ‘trained’ cells and with trained cells following restimulation. H3K27ac, histone 3 lysine 27 acetylation; H3K4me, histone 3 lysine 4 methylation; H3K4me3, histone 3 lysine 4 trimethylation.