Meyoid-specific deficiency of Glutamine Synthetase Aggravates LPS/D-GalN-induced liver injury via the activation of monocyte-derived macrophages

Glutamine synthase (Glul) is a key enzyme to synthesize glutamine, but its function in acute liver injury (ALI) remains unclear. Here, we investigated the regulatory role of Glul on immnuity in LPS/D-GalN-induced ALI. The study firstly found that the expression of Glul in myeloid cells was inhibited following LPS/D-GalN challenge. Then myeloid-specific knockout Glul mice were generated, which showed more severe ALI and higher mortality due to the activation of monocyte-derived macrophages (MoMFs) and the secretion of CCL2, as well as the recruitment of CCR2+ monocytes. Notably, liver injury can be relieved with adeno-associated virus (AAV)-mediated hepatic delivery of Glul via tail vein injection in mice. In conclusion, this research validates the protective effect of Glul against ALI. Overall design: we extracted RNA from liver tissues in Glullflox/flox and Glul?lyz2 mice treated with LPS/D-GalN or H2O and then performed mRNA transcriptome analysis