In vivo screening for essential metabolic mediators in mouse model of lung inflammation using AAV9-ME CRISPR library

Timely termination of innate immune response and resolution of inflammation is critical for preventing tissue damage and keeping homeostasis. Immunometabolism is verified to be important in innate immunity and inflammation. However, metabolic processes and related enzymes involved in inflammatory resolution remain largely unknown. To identify the key mediators in the metabolic regulation of inflammation resolution, we generated an AAV9-ME CRISPR library containing 17090 sgRNAs targeting 2682 mouse metabolic genes and performed an in vivo CRISPR screen in influenza virus (IAV) infection-induced lung inflammation model in Sftpc-Cas9 mice. We found that a very long chain fatty acid elongase, ELOVL5, could promote the resolution of lung inflammation. These results provide evidence for the metabolic gene-mediated regulation of immune inflammation and also insights for treating inflammatory diseases through manipulating metabolism. Overall design: Next-generation sequencing of IAV_screen and Input sample, RNA-seq of type 2 AEC from mice infected with IAV for different times: Day0: C1,C2; Day7: I1,I2; Day12: R1,R2.