KDM7A restrains fibrotic macrophage polarization and lung fibrosis. Loss of Kdm7a drives transcriptional and metabolic reprogramming toward Fib-Mac states, expands Fib-Macs, and exacerbates bleomycin-induced fibrosis, consistent with reduced KDM7A in human disease. Mechanistically, Kdm7a loss increases H3K27me2 at the Tlr8 enhancer, reduces TLR8 expression, and promotes Fib-Mac polarization.
- Naofumi Funagura
- Tomoaki Koga
- Mitsuyoshi Nakao