Fig. 4
From: Activation of immune signals during organ transplantation
Trained immunity. a, b Exogenous or endogenous stimuli induce long-term functional reprogramming of innate immune cells, resulting in a stronger (a) or weaker (b) response to the second non-specific stimulation after the innate immune cells recover to the inactive state. c The inducer stimulates hematopoietic stem cells and myeloid progenitor cells (central) as well as blood monocytes and tissue macrophages (peripheral) to generate trained immunity. The reactive changes of inflammatory gene subsets in myeloid cells are mediated by metabolic and epigenetic reprogramming. Receptor signals from myeloid cells activate the AKT/mTOR/HIF-1α pathway, promoting the glycolysis. Its metabolite pyruvate enters the tricarboxylic acid cycle (TCA cycle), forming metabolic intermediates: Acetyl-CoA, Fumarate, Succinate, α-ketoglutarate, NAD+. These metabolic intermediates directly or indirectly mediate histone acetylation and methylation (H3K4me3, H3K4me1, H3K27ac)
