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. we extracted RNA from liver tissues in Glullflox/flox and GlulΔlyz2 mice treated with LPS/D-GalN or H2O and then performed mRNA transcriptome analysis