CD300e-mediated nutrient sensing regulates cellular metabolism in macrophages

CD300e is an immune receptor expressed on myeloid cells, whose downstream signalling pathway remains poorly characterized. In our previous work, we demonstrated that metabolically activated macrophages (MMe) from CD300e-/- mice exhibit reduced glucose and fatty acid uptake together with impaired mitochondrial respiration and glycolytic capacity, indicating a metabolic dysfunction. However, the molecular mechanisms underlying this phenotype remained unknown. In the present study, we investigated how CD300e deficiency affects mitochondrial homeostasis and intracellular signalling in MMe. Microscopy and biochemical analyses revealed altered mitochondrial morphology and reduced mitochondrial mass in CD300e-/- MMe, consistent with impaired oxidative phosphorylation. To identify the signalling pathways responsible for this metabolic defect, we examined regulators of cellular metabolism and protein synthesis. CD300e-deficient MMe displayed reduced activation of the AKT/mTOR pathway, accompanied by decreased global protein translation. These findings identify CD300e as an upstream regulator of the AKT/mTORC1 axis, linking receptor signalling to mitochondrial homeostasis and translational control in metabolically activated macrophages. Together with our previous findings, they provide a mechanistic explanation for the impaired metabolic phenotype associated with CD300e deficiency.