Macrophages that clear apoptotic cells (efferocytosis) proliferate to enhance tissue repair and resolution. Here, we find that a previously elucidated nucleotide ‘cargo’ proliferation pathway that increases Myc mRNA is complemented by efferocytosis-induced lactate, which stabilizes Myc protein through SIRT1-mediated Myc protein deacetylation.
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References
Gerlach, B. D. et al. Efferocytosis induces macrophage proliferation to help resolve tissue injury. Cell Metab. 33, 2445–2463 (2021). To our knowledge, this paper was the first to report the nucleotide ‘cargo’ pathway driving EIMP.
Morioka, S. et al. Efferocytosis induces a novel SLC program to promote glucose uptake and lactate release. Nature 563, 714–718 (2018). To our knowledge, this paper was the first to report that efferocytosis triggers increased glycolysis and lactate production in macrophages.
Schilperoort, M. et al. PFKFB2-mediated glycolysis promotes lactate-driven continual efferocytosis by macrophages. Nat. Metab. 5, 431–444 (2023). To our knowledge, this paper was the first to show that efferocytosis-induced glycolysis is transient, as opposed to the prolonged glycolytic shift observed in pro-inflammatory macrophages.
Vadevoo, S. M. P. et al. The macrophage odorant receptor Olfr78 mediates the lactate-induced M2 phenotype of tumor-associated macrophages. Proc. Natl Acad. Sci. USA 118, e2102434118 (2021). This paper shows the role of GPR132 in facilitating lactate-induced polarization of macrophages to a pro-resolving phenotype.
Tawakol, A. et al. HIF-1α and PFKFB3 mediate a tight relationship between proinflammatory activation and anerobic metabolism in atherosclerotic macrophages. Arterioscler. Thromb. Vasc. Biol. 35, 1463–1471 (2015). This paper shows that in pro-inflammatory conditions such as atherosclerosis, macrophages undergo a prolonged glycolytic shift by transcriptional mechanisms that increase lactate production.
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This is a summary of: Ngai, D. et al. Efferocytosis-induced lactate enables the proliferation of pro-resolving macrophages to mediate tissue repair. Nat. Metab. https://doi.org/10.1038/s42255-023-00921-9 (2023).
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Lactate helps in tissue repair by promoting efferocytosis-induced macrophage proliferation. Nat Metab 5, 2045–2046 (2023). https://doi.org/10.1038/s42255-023-00920-w
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DOI: https://doi.org/10.1038/s42255-023-00920-w
