Kupffer Cells Regulate iNKT Cells Through Il‐12 to Mitigate the Extent of APAP‐Induced Damage in the Liver

ABSTRACT To explore the innate immune response in the occurrence and development of APAP‐induced drug‐induced liver injury and the biological effect caused by the interaction between immune cells through real‐time, in vivo analysis. We used conventional molecular biology technology and multi‐photon confocal live imaging to explore the effect of the interactive dialogue between iNKT and Kupffer cells on neutrophil recruitment in the occurrence and development of APAP‐induced liver injury. iNKT cell deficient mice were more prone to liver injury induced by excessive APAP, and the degree of liver injury was more severe. After injury, iNKT cells were recruited into the liver and showed IL‐4 high expression activation mode. Furthermore, we also found that Kupffer cells in APAP induced liver injury produce M1 polarisation and highly expressed IL‐12, that Kupffer cells regulate the activation of iNKT cells through IL‐12; and that IL‐4 produced by iNKT cells in the liver can also inhibit inflammatory damage caused by neutrophil recruitment. Our study shows that Kupffer cells produce IL‐12 and promote activated iNKT cells to produce more IL‐4, and inhibit the recruitment of neutrophils, thereby reducing the degree of liver inflammatory injury induced by APAP.