Socs3-mediated inhibition of inflammation by Ezh2 deficiency. Macrophage Ezh2 deficiency reduces suppressive H3K27Me3 marks at the Socs3 transcriptional start site and distal enhancer, resulting in increased Socs3 expression. Cytosolic Socs3 inhibits proinflammatory gene expression by targeting the TLR-induced MyD88–TRAF6–NF-κB signaling pathway. Socs3 enhances TRAF6 ubiquitination, resulting in its proteasomal degradation, and thereby suppresses activation of NF-κB–dependent inflammatory genes. The figure was made with use of Smart Servier Medical Art, licensed under a Creative Common Attribution 3.0 Unported License.