Cited by 1,223Phagocytosis and Immune RegulationCell death mechanisms and regulationAutophagy in Disease and Therapy

Apoptotic cell clearance: basic biology and therapeutic potential

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Poon, Ivan K. H., Lucas, Christopher D., Rossi, Adriano G., Ravichandran, Kodi S.·2014·Nature Reviews Immunology

Abstract

The prompt removal of apoptotic cells by phagocytes is important for maintaining tissue homeostasis. The molecular and cellular events that underpin apoptotic cell recognition and uptake, and the subsequent biological responses, are increasingly better defined. The detection and disposal of apoptotic cells generally promote an anti-inflammatory response at the tissue level, as well as immunological tolerance. Consequently, defects in apoptotic cell clearance have been linked with various inflammatory diseases and autoimmunity. Conversely, under certain conditions, such as the killing of tumour cells by specific cell-death inducers, the recognition of apoptotic tumour cells can promote an immunogenic response and antitumour immunity. Here, we review the current understanding of the complex process of apoptotic cell clearance in physiology and pathology, and discuss how this knowledge could be harnessed for new therapeutic strategies.

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  • Both signaling pathways governing apoptotic cell removal converge in activation of Rho GTPases such as Rac1 to promote actin polymerization, membrane ruffling, and phagocytosis.

    “Both pathways finally converge in the activation of Rho GTPases such as Rac1 to promote actin polymerization, membrane ruffling, and phagocytosis (131, 132).”

    From Macrophage defense mechanisms against intracellular bacteria (2015) · cites this paper as [132]

  • Apoptotic cells release 'find me' and expose 'eat me' signals such as PS, lysoPS, cardiolipin, calreticulin, CD31, fractalkine, and small amounts of nucleotides, which are recognized by phagocytes promoting efferocytosis.

    “Apoptotic cells release ‘find me’ and expose ‘eat me’ signals such as PS, lysoPS, cardiolipin, calreticulin, and CD31, as well as the chemokine fractalkine (CX3CL1 as recognized by CX3CR1) and small amounts of nucleotides (ATP, UTP). These ligands are recognized by phagocytes promoting efferocytosis (131, 132).”

    From Macrophage defense mechanisms against intracellular bacteria (2015) · cites this paper as [132]

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Authors
Poon, I. K. H., Lucas, C. D., Rossi, A. G., & Ravichandran, K. S.
Affiliations
  • La Trobe University (AU)
  • Centre for Inflammation Research (GB)
  • University of Virginia (US)
Corresponding author
  • Rossi, Adriano G.
  • Ravichandran, Kodi S.
Venue
Nature Reviews Immunology
Published
2014-01-31
Volume
14
Issue
3
Pages
166-180
ISSN
  • 1474-1733 (ISSN-L)
  • 1474-1741
OpenAlex
W2150334056
Cited by
1,223
References
197
Citations by year
2026: 69 · 2025: 87 · 2024: 100 · 2023: 97 · 2022: 112 · 2021: 120 · 2020: 115 · 2019: 97 · 2018: 106 · 2017: 106 · 2016: 101 · 2015: 87 · 2014: 23 · 2013: 2
FWCI
10.31
Type
journal article
Language
en
Open access
Locations
  • Nature reviews. Immunology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
Funders
  • Wellcome Trust (WT094415)
  • Medical Research Council (MR/K013386/1)
  • National Institute of Mental Health (R01MH096484, MH096484)
  • National Institute of General Medical Sciences (GM-64709, R01GM107848, R01GM064709, GM107848)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD074981, R01HD074981)
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
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
Keywords
efferocytosis, phagocytes, apoptotic cell recognition, tissue homeostasis, immune tolerance, inflammation, autoimmunity, immunogenic cell death, antitumor immunity
MeSH terms
Animals, Humans, Immune Tolerance, Inflammation, Lupus Erythematosus, Systemic, Macrophages, Neoplasms, Phagocytes, Phagocytosis, Autoimmunity, Apoptosis, Atherosclerosis, Mice

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