Evidence map›Paper›PMID 39242914›Full record

ArticleNature metabolism2024

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

Santosh R Sukka, Patrick B Ampomah, Lancia N F Darville, David Ngai, Xiaobo Wang, George Kuriakose, Yuling Xiao, Jinjun Shi, John M Koomen, Robert H McCusker and 1 more

Erratum issuedAbstract read
In one paragraph

Article in Nature metabolism, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 52 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
52citing papers in PubMed, 2 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

52 citing papers in PubMed, 2 syntheses or guidelines pooled it.

  1. Hyperprogressive disease in carcinoma induced by immune checkpoint inhibitor therapy: a systematic review.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
    Pooled it
  2. Pooled it
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Mechanistic elucidation ofJournal of ginseng research · 2026
    Article
  10. Article
  11. Review
  12. Article
  13. Defective efferocytosis in diabetes: molecular mechanisms and emerging therapeutic strategies.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026
    Review
  14. Review
  15. Article
  16. Review
  17. Article
  18. Article
  19. Bon appétit, your phagocyte.Cell death discovery · 2026
    Review
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors.

Santosh R SukkaDepartment of Medicine, Columbia University Irving Medical Center, New York, NY, USA. srs2302@columbia.edu.ORCID http://orcid.org/0000-0003-2334-4685
Patrick B AmpomahDepartment of Medicine, Columbia University Irving Medical Center, New York, NY, USA.ORCID http://orcid.org/0000-0003-0561-1145
Lancia N F DarvilleProteomics and Metabolomics Core, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
David NgaiDepartment of Medicine, Columbia University Irving Medical Center, New York, NY, USA.
Xiaobo WangDepartment of Medicine, Columbia University Irving Medical Center, New York, NY, USA.ORCID http://orcid.org/0000-0001-6044-914X
George KuriakoseDepartment of Medicine, Columbia University Irving Medical Center, New York, NY, USA.
Yuling XiaoCenter for Nanomedicine and Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Jinjun ShiCenter for Nanomedicine and Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0001-9200-5068
John M KoomenProteomics and Metabolomics Core, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.ORCID http://orcid.org/0000-0002-3818-1762
Robert H McCuskerDepartment of Animal Sciences, Integrative Immunology and Behavior Program and Neuroscience Program, University of Illinois at Urbana-Champaign, Urbana, IL, USA.ORCID http://orcid.org/0000-0001-8006-3228
Ira TabasDepartment of Medicine, Columbia University Irving Medical Center, New York, NY, USA. iat1@columbia.edu.ORCID http://orcid.org/0000-0003-3429-1515

Funding

Tumor Biology and Microenvironment ProgramP30CA013696 · NCI · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI Anil K Rustgi · 1985 to 2026
$115.3M
TRANSLATIONAL RESEARCHP30CA076292 · NCI · UNIVERSITY OF SOUTH FLORIDA · PI Christine O'Connell · 1998 to 2026
$93.5M
TTC39B in obesity and atherosclerosisP01HL087123 · NHLBI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI TABAS, IRA A · 2007 to 2022
$31.2M
Mouse and Human Atherosclerotic TissueP01HL172741 · NHLBI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI ALAN richard TALL · 2024 to 2026
$9.5M
A Mechanistic and Translational Research Program Linking Impaired Resolution, Defective Efferocytosis, and Clonal Hematopoiesis to the Formation of Clinically Dangerous Atherosclerotic PlaquesR35HL145228 · NHLBI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI TABAS, IRA A · 2019 to 2025
$6.8M
Long-Acting RNAi Therapy for Atherosclerosis and Insulin ResistanceR01HL159012 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI SHI, JINJUN · 2021 to 2024
$2.7M
BD Biosciences InfluxS10OD020056 · OD · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI SNOECK, HANS-WILLEM E · 2015 to 2015
$600k
MULTIPHOTON CONFOCAL MICROSCOPES10RR025686 · NCRR · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI PON, LIZA A · 2010 to 2010
$499k
Becton Dickinson LSR II Analytical Flow CytometerS10RR027050 · NCRR · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI CLYNES, RAPHAEL A. · 2011 to 2011
$413k
NCI NIH HHS P30 CA013696NCI NIH HHS P30 CA076292NCRR NIH HHS S10 RR025686NCRR NIH HHS S10 RR027050NHLBI NIH HHS P01 HL087123NHLBI NIH HHS P01 HL172741NHLBI NIH HHS R01 HL159012NHLBI NIH HHS R35 HL145228NIH HHS S10 OD020056U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) HL087123U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) HL145228U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) HL159012
6 · The paper itself

Abstract

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.

Indexed as

Indoleamine-Pyrrole 2,3,-DioxygenaseMacrophagesPhagocytosisReceptors, Aryl HydrocarbonTryptophanAnimalsApoptosisAtherosclerosisEfferocytosisInflammationKynurenineMiceIDO1 protein, mouseIndoleamine-Pyrrole 2,3,-DioxygenaseKynurenineReceptors, Aryl HydrocarbonTryptophan

Identifiers

PMID39242914
PMCPMC11734744

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.