Efferocytosis-induced lactate enables the proliferation of pro-resolving macrophages to mediate tissue repair.
Journal
Nature metabolism
ISSN: 2522-5812
Titre abrégé: Nat Metab
Pays: Germany
ID NLM: 101736592
Informations de publication
Date de publication:
27 Nov 2023
27 Nov 2023
Historique:
received:
15
05
2023
accepted:
05
10
2023
medline:
28
11
2023
pubmed:
28
11
2023
entrez:
27
11
2023
Statut:
aheadofprint
Résumé
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.
Identifiants
pubmed: 38012414
doi: 10.1038/s42255-023-00921-9
pii: 10.1038/s42255-023-00921-9
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : R35-HL145228
Organisme : American Heart Association (American Heart Association, Inc.)
ID : 900337
Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Nature Limited.
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