{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Ngai D"],"funding":["American Heart Association","NCRR NIH HHS","NHLBI NIH HHS","NCI NIH HHS","NIH HHS","U.S. Department of Health & Human Services | National Institutes of Health"],"pagination":["2206-2219"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10782856"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["5(12)"],"pubmed_abstract":["The clearance of apoptotic cells by macrophages (efferocytosis) prevents necrosis and inflammation and activates pro-resolving pathways, including continual efferocytosis. A key resolution process in vivo is efferocytosis-induced macrophage proliferation (EIMP), in which apoptotic cell-derived nucleotides trigger Myc-mediated proliferation of pro-resolving macrophages. Here we show that EIMP requires a second input that is integrated with cellular metabolism, notably efferocytosis-induced lactate production. Lactate signalling via GPR132 promotes Myc protein stabilization and subsequent macrophage proliferation. This mechanism is validated in vivo using a mouse model of dexamethasone-induced thymocyte apoptosis, which elevates apoptotic cell burden and requires efferocytosis to prevent inflammation and necrosis. Thus, EIMP, a key process in tissue resolution, requires inputs from two independent processes: a signalling pathway induced by apoptotic cell-derived nucleotides and a cellular metabolism pathway involving lactate production. These findings illustrate how seemingly distinct pathways in efferocytosing macrophages are integrated to carry out a key process in tissue resolution."],"journal":["Nature metabolism"],"pubmed_title":["Efferocytosis-induced lactate enables the proliferation of pro-resolving macrophages to mediate tissue repair."],"pmcid":["PMC10782856"],"funding_grant_id":["S10 OD020056","S10 RR027050","R35-HL145228","P01 HL087123","900337","R35 HL145228","P30 CA013696"],"pubmed_authors":["Schilperoort M","Tabas I","Ngai D"],"additional_accession":[]},"is_claimable":false,"name":"Efferocytosis-induced lactate enables the proliferation of pro-resolving macrophages to mediate tissue repair.","description":"The clearance of apoptotic cells by macrophages (efferocytosis) prevents necrosis and inflammation and activates pro-resolving pathways, including continual efferocytosis. A key resolution process in vivo is efferocytosis-induced macrophage proliferation (EIMP), in which apoptotic cell-derived nucleotides trigger Myc-mediated proliferation of pro-resolving macrophages. Here we show that EIMP requires a second input that is integrated with cellular metabolism, notably efferocytosis-induced lactate production. Lactate signalling via GPR132 promotes Myc protein stabilization and subsequent macrophage proliferation. This mechanism is validated in vivo using a mouse model of dexamethasone-induced thymocyte apoptosis, which elevates apoptotic cell burden and requires efferocytosis to prevent inflammation and necrosis. Thus, EIMP, a key process in tissue resolution, requires inputs from two independent processes: a signalling pathway induced by apoptotic cell-derived nucleotides and a cellular metabolism pathway involving lactate production. These findings illustrate how seemingly distinct pathways in efferocytosing macrophages are integrated to carry out a key process in tissue resolution.","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Dec","modification":"2025-04-04T01:17:59.256Z","creation":"2025-04-04T01:17:59.256Z"},"accession":"S-EPMC10782856","cross_references":{"pubmed":["38012414"],"doi":["10.1038/s42255-023-00921-9"]}}