H3K9 demethylase KDM3A potentiates interferon signaling and macrophage-driven inflammation in atherosclerosis.

KDM3A-mediated H3K9 demethylation enhances interferon signaling in macrophages, and hematopoietic Kdm3a deficiency in atherosclerotic mice reduces lesion size and neutrophil recruitment.

• Why it matters: Atherosclerosis inflammation is shaped by epigenetic programs in macrophages, but how H3K9 methylation control tunes interferon-driven activation and plaque progression is unclear.
• What they did: The study mapped KDM3A-dependent H3K9 demethylation to increased chromatin accessibility at interferon loci, then tested hematopoietic Kdm3a deficiency in a mouse atherosclerosis model and used in vitro/in vivo macrophage assays.
• The result: Kdm3a-deficient macrophages had impaired chemokine secretion and reduced neutrophil recruitment, while KDM3A knockdown in primary human macrophages suppressed IFN responses and KDM3A gene signatures were enriched in IFN-inducible cells from human plaques.

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