The many ways tissue phagocytes respond to dying cells
Open accessAbstract
Summary: Apoptosis is an important component of normal tissue physiology, and the prompt removal of apoptotic cells is equally essential to avoid the undesirable consequences of their accumulation and disintegration. Professional phagocytes are highly specialized for engulfing apoptotic cells. The recent ability to track cells that have undergone apoptosis in situ has revealed a division of labor among the tissue resident phagocytes that sample them. Macrophages are uniquely programmed to process internalized apoptotic cell‐derived fatty acids, cholesterol and nucleotides, as a reflection of their dominant role in clearing the bulk of apoptotic cells. Dendritic cells carry apoptotic cells to lymph nodes where they signal the emergence and expansion of highly suppressive regulatory CD 4 T cells. A broad suppression of inflammation is executed through distinct phagocyte‐specific mechanisms. A clever induction of negative regulatory nodes is notable in dendritic cells serving to simultaneously shut down multiple pathways of inflammation. Several of the genes and pathways modulated in phagocytes in response to apoptotic cells have been linked to chronic inflammatory and autoimmune diseases such as atherosclerosis, inflammatory bowel disease and systemic lupus erythematosus. Our collective understanding of old and new phagocyte functions after apoptotic cell phagocytosis demonstrates the enormity of ways to mediate immune suppression and enforce tissue homeostasis.
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A large fraction of cerebellar microglia-enriched genes encode proteins involved in apoptotic cell detection, engulfment, clearance of cell debris, and lipid/protein catabolism, and have been shown to support clearance activity in phagocytic macrophages in peripheral tissues.
“A large fraction of the cbMg-enriched genes, including Apoe, Axl, Colec12, Cd74, Lilrb4, Mrc1, and Ms4a7 (Fig. 1d,e, Supplementary Fig. 5a,b, Supplementary Table 3), encode proteins involved in apoptotic cell detection, engulfment, clearance of cell debris, and lipid/protein catabolism and have been shown to support clearance activity in phagocytic macrophages in peripheral tissues21.”
From Epigenetic regulation of brain region-specific microglia clearance activity (2018) · cites this paper as [21]
A significant fraction of cerebellar microglia-expressed genes have been implicated in detection, engulfment, and catabolism of debris in peripheral macrophages carrying out cell clearance and in microglia associated with ageing and neurodegeneration.
“In particular, a significant fraction of the cbMg-expressed genes have been implicated in the detection, engulfment, and catabolism of debris both in peripheral macrophages carrying out cell clearance21 as well as in microglia associated with ageing and neurodegeneration11–13.”
From Epigenetic regulation of brain region-specific microglia clearance activity (2018) · cites this paper as [21]
Because cbMg show little inflammatory gene activation, their clearance activity may oppose or suppress inflammatory gene activation, similar to peripheral macrophages.
“The lack of inflammatory gene activation in cbMg suggests that the microglia clearance activity may antagonize/suppress the activation of inflammatory genes in a fashion that has been observed in peripheral macrophages21,23.”
From Epigenetic regulation of brain region-specific microglia clearance activity (2018) · cites this paper as [21]
Efferocytosis is a multi-step process comprising recognition of eat-me signals, engulfment of cells/debris, degradation of engulfed material, and excretion of metabolic products.
“This process, often referred to as efferocytosis, is a multi-step process: (i) the recognition of “eat-me” signals presented by apoptotic cells, (ii) engulfment of cells/debris, (iii) degradation of engulfed material, and (iv) excretion of metabolic products21.”
From Epigenetic regulation of brain region-specific microglia clearance activity (2018) · cites this paper as [21]
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References 291 · Cited by 84
- Authors
- Blander, J. M.
- Affiliations
- Cornell University (US)
- Corresponding author
- Blander, J. Magarian
- ORCID
- Blander, J. Magarian
- Venue
- Immunological Reviews
- Publisher
- Wiley
- Published
- 2017-04-30
- Volume
- 277
- Issue
- 1
- Pages
- 158-173
- ISSN
- 0105-2896 (ISSN-L)
- 1600-065X
- PMC
- PMC5721677
- OpenAlex
- W2610699844
- Cited by
- 84
- References
- 291
- Citations by year
- 2026: 7 · 2025: 8 · 2024: 8 · 2023: 7 · 2022: 10 · 2021: 9 · 2020: 11 · 2019: 13 · 2018: 4 · 2017: 7
- FWCI
- 0.98
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Immunological Reviews (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (DK072201)
- National Institute of Allergy and Infectious Diseases (AI123284, AI127658)
- Burroughs Wellcome Fund
- Leukemia and Lymphoma Society
- 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 › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- efferocytosis, phagocytes, macrophages, dendritic cells, regulatory T cells, immunosuppression, inflammation reduction, tissue homeostasis, atherosclerosis, inflammatory bowel disease, systemic lupus erythematosus, autoimmune disease, chronic inflammation
- MeSH terms
- Animals, Cholesterol, Dendritic Cells, Fatty Acids, Homeostasis, Humans, Immune Tolerance, Lupus Erythematosus, Systemic, Nucleotides, Phagocytes, Phagocytosis, Inflammatory Bowel Diseases, Apoptosis, Atherosclerosis
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