Alveolar epithelial cells mitigate neutrophilic inflammation in acute lung injury through regulating mitochondrial fatty acid oxidation

Carnitine palmitoyltransferase 1a (CPT1a) is the key regulator of mitochondrial long-chain fatty acid beta-oxidation (LCFAO). However, the functional significance of AT2 cell-specific LCFAO at baseline and during acute lung injury (ALI) is not fully understood. In this study, Murine models of AT2 cell-specific Cpt1a deletion were generated for investigating the role of CPT1a in regulating AT2 cell function and the severity of lipopolysaccharide-induced murine ALI models. AT2 cells were isolated from the lungs from mice with AT2 cell-specific Cpt1a deletion (Cpt1a-KO) and the control (Sftpc-CreERt2 +/-) at baseline and 24 hours after intra-tracheal LPS administration. To investigate whether impaired LCFAO in AT2 cells regulates the responses of alveolar macrophages in ALI, we also isolated alveolar macrophages from Cpt1a-KO and control mice at 4 hours after intra-tracheal LPS administration, and alveolar macrophages from control mice at baseline. Alveolar macrophages from 2 mice were pooled to make one sample for trancriptomic analysis.