GSE119273
Efferocytosis induces a novel SLC program to promote glucose uptake and lactate release
On a daily basis, we turnover billions of apoptotic cells that are removed by professional and non-professional phagocytes1-10. While characterizing the transcriptional program of phagocytes, we discovered a novel solute carrier family (SLC) gene signature (33 SLC members) that is specifically modified during engulfment of apoptotic cells (efferocytosis) but not during antibody-mediated phagocytosis. When we assessed the functional relevance of these SLCs, we noted robust induction of an aerobic glycolysis program in engulfing phagocytes, initiated by SLC2A1-mediated glucose uptake, and suppression of oxidative phosphorylation program. Interestingly, the different steps of phagocytosis10,11, i.e. smell ('find-me' signals / sensing factors released by apoptotic cells), taste (phagocyte- apoptotic cell contact), and ingestion (corpse internalization), activated different molecules to promote this glycolytic process. Further, lactate, a natural by-product of aerobic glycolysis12,13, was released from engulfing phagocytes via SLC16A1, an SLC member activated after corpse uptake. While glycolysis within phagocytes contributed to actin polymerization and the continued uptake of corpses, the lactate released via SLC16A1 influenced the establishment of an anti-inflammatory environment. Collectively, these data reveal a novel SLC program activated during efferocytosis, identify a previously unknown reliance on aerobic glycolysis during apoptotic cell uptake, and that glycolytic byproducts of efferocytosis can also influence other cells in the microenvironment. Overall design: The experiment consisted of two conditions: Phagocytes (LR73 cells) alone or co-cultured with apoptotic Jurkat lymphoma cells. Each condition consisted of four biological replicates.