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. 2021 May 12;12:669566. doi: 10.3389/fimmu.2021.669566

Figure 3.

Figure 3

Mechanisms associated with epigenetic regulation/modification whereby iron shapes macrophage polarization. Iron supplementation may reduce miR-29a expression to block the activation of SOCS1/STAT6 signal pathway, inhibiting TAM polarization (A). Iron could promote M1-like macrophage polarization by increasing miR-214 expression (B). Iron could increase the enzyme activity of JMJD3 to demethylate H3K27me3, relieving the transcriptional silencing of LPS-induced genes and facilitating M1-like macrophage polarization (C). Iron might promote macrophages toward pro-inflammatory phenotype through demethylating H4K20me3 by enhancing the enzyme activity of HR23A (D). Iron deficiency might cause the loss of H3K9Ac and H3K4me3 to reduce hepcidin expression, inhibiting M1-like macrophage polarization (E). Iron deficiency inhibits M1 activation (e.g., pro-inflammatory responses) possibly through increasing HDAC1 binding to the related genes (F). Iron deficiency inhibits M1-like phenotype by lowering hepcidin expression via enhancing HDAC3 binds chromatin at the hepcidin locus (G). H3K27me3, histone 3 lysine 27 trimethylation; H4K20me3, histone 4 lysine 20 trimethylation; HDAC, histone deacetylase; SOCS1, suppressor of cytokine signaling 1. “↑”, increase; “↓”, decrease. Question mark means that the mechanism needs experimental confirmation.