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Drugging the efferocytosis process: concepts and opportunities
Open accessAbstract
The daily removal of billions of apoptotic cells in the human body via the process of efferocytosis is essential for homeostasis. To allow for this continuous efferocytosis, rapid phenotypic changes occur in the phagocytes enabling them to engulf and digest the apoptotic cargo. In addition, efferocytosis is actively anti-inflammatory and promotes resolution. Owing to its ubiquitous nature and the sheer volume of cell turnover, efferocytosis is a point of vulnerability. Aberrations in efferocytosis are associated with numerous inflammatory pathologies, including atherosclerosis, cancer and infections. The recent exciting discoveries defining the molecular machinery involved in efferocytosis have opened many avenues for therapeutic intervention, with several agents now in clinical trials.
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“efferocytosis in other settings can promote fibrosis as part of the tissue resolution process, for example, by secreting TGF-β1 (12, 13).”
From Impaired TIM4-mediated efferocytosis by liver macrophages contributes to fibrosis in metabolic dysfunction–associated steatohepatitis (2025) · cites this paper as [13]
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“While some progress has been made with respect to the Fractalkine receptor (CX3C motif chemokine receptor 1), Axl, MerTK, CD47 and Tim4/3, no approaches have thus far been clinically approved (64).”
From Cholesterol efflux protein, ABCA1, supports anticancer functions of myeloid immune cells (2026) · cites this paper as [64]
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“The accumulation of dead cells in disease settings indicates impaired clearance of dead cells by macrophages (“efferocytosis”) (12, 13).”
From Impaired TIM4-mediated efferocytosis by liver macrophages contributes to fibrosis in metabolic dysfunction–associated steatohepatitis (2025) · cites this paper as [13]
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“Efferocytosis not only prevents dead cell accumulation but also reprograms macrophages to execute tissue resolution functions, and impaired efferocytosis contributes to many human chronic inflammatory diseases (12, 13).”
From Impaired TIM4-mediated efferocytosis by liver macrophages contributes to fibrosis in metabolic dysfunction–associated steatohepatitis (2025) · cites this paper as [13]
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“It is seen as a major hurdle to using antigen presenting cells in cell-based therapies (61–64).”
From Cholesterol efflux protein, ABCA1, supports anticancer functions of myeloid immune cells (2026) · cites this paper as [64]
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Metadata
- Authors
- Mehrotra, P., & Ravichandran, K. S.
- Affiliations
- VIB-UGent Center for Inflammation Research (BE)
- Washington University in St. Louis (US)
- Corresponding author
- Ravichandran, Kodi S.
- Venue
- Nature Reviews Drug Discovery
- Published
- 2022-06-01
- Volume
- 21
- Issue
- 8
- Pages
- 601-620
- ISSN
- 1474-1776 (ISSN-L)
- 1474-1784
- PMC
- PMC9157040
- OpenAlex
- W4281737563
- Cited by
- 459
- References
- 231
- Citations by year
- 2026: 130 · 2025: 153 · 2024: 104 · 2023: 66 · 2022: 6
- FWCI
- 8.88
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Nature Reviews Drug Discovery (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion)
- Funders
- National Heart, Lung, and Blood Institute (P01HL120840)
- National Institute of General Medical Sciences (R35GM122542)
- National Institute of Allergy and Infectious Diseases (R01AI159551)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Keywords
- efferocytosis, phagocytes, anti-inflammatory mechanism, inflammation resolution, therapeutic target, atherosclerosis, cancer, infection
- MeSH terms
- Homeostasis, Humans, Phagocytes, Phagocytosis, Apoptosis, Atherosclerosis
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