A long noncoding RNA regulates inflammation resolution by mouse macrophages through fatty acid oxidation activation

Proper resolution of inflammation is vital for repair and restora- tion of homeostasis after tissue damage, and its dysregulation underlies various noncommunicable diseases, such as cardiovas- cular and metabolic diseases. Macrophages play diverse roles throughout initial inflammation, its resolution, and tissue repair. Differential metabolic reprogramming is reportedly required for induction and support of the various macrophage activation states. Here we show that a long noncoding RNA (lncRNA), lncFAO , con- tributes to inflammation resolution and tissue repair in mice by pro- moting fatty acid oxidation (FAO) in macrophages. lncFAO is induced late after lipopolysaccharide (LPS) stimulation of cultured macro- phages and in Ly6C hi monocyte-derived macrophages in damaged tissue during the resolution and reparative phases. We found that lncFAO directly interacts with the HADHB subunit of mitochondrial trifunctional protein and activates FAO. lncFAO deletion impairs res- olution of inflammation related to endotoxic shock and delays reso- lution of inflammation and tissue repair in a skin wound. These results demonstrate that by tuning mitochondrial metabolism, lncFAO acts as a node of immunometabolic control in macrophages during the resolution and repair phases of inflammation.