Efferocytosis drives a tryptophan metabolism pathway in macrophages to promote tissue resolution.

Autor: Sukka SR; Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA. srs2302@columbia.edu., Ampomah PB; Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA., Darville LNF; Proteomics and Metabolomics Core, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA., Ngai D; Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA., Wang X; Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA., Kuriakose G; Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA., Xiao Y; Center for Nanomedicine and Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Shi J; Center for Nanomedicine and Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Koomen JM; Proteomics and Metabolomics Core, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA., McCusker RH; Department of Animal Sciences, Integrative Immunology and Behavior Program and Neuroscience Program, University of Illinois at Urbana-Champaign, Urbana, IL, USA., Tabas I; Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA. iat1@columbia.edu.; Departments of Physiology and Cell Biology, Columbia University Irving Medical Center, New York, NY, USA. iat1@columbia.edu.
Jazyk: angličtina
Zdroj: Nature metabolism [Nat Metab] 2024 Sep; Vol. 6 (9), pp. 1736-1755. Date of Electronic Publication: 2024 Sep 06.
DOI: 10.1038/s42255-024-01115-7
Abstrakt: Macrophage efferocytosis prevents apoptotic cell (AC) accumulation and triggers inflammation-resolution pathways. The mechanisms linking efferocytosis to resolution often involve changes in macrophage metabolism, but many gaps remain in our understanding of these processes. We now report that efferocytosis triggers an indoleamine 2,3-dioxygenase-1 (IDO1)-dependent tryptophan (Trp) metabolism pathway that promotes several key resolution processes, including the induction of pro-resolving proteins, such interleukin-10, and further enhancement of efferocytosis. The process begins with upregulation of Trp transport and metabolism, and it involves subsequent activation of the aryl hydrocarbon receptor (AhR) by the Trp metabolite kynurenine (Kyn). Through these mechanisms, macrophage IDO1 and AhR contribute to a proper resolution response in several different mouse models of efferocytosis-dependent tissue repair, notably during atherosclerosis regression induced by plasma low-density lipoprotein (LDL) lowering. These findings reveal an integrated metabolism programme in macrophages that links efferocytosis to resolution, with possible therapeutic implications for non-resolving chronic inflammatory diseases, notably atherosclerosis.
(© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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