Engulfment signals and the phagocytic machinery for apoptotic cell clearance

Park, Seung Yoon; Kim, In San

doi:10.1038/emm.2017.52

Cited by 127 publications

(120 citation statements)

References 130 publications

(145 reference statements)

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“…Importantly, phagocytosis is the process responsible for the induction of the pro-to anti-phenotypical switch in MPs. While numerous studies investigated the mechanisms involved in the progression or inhibition of phagocytosis, how apoptotic cells attract MPs and how MPs recognize them is still unknown [10,14,15,50,51]. In our study, phagocytosis of LysM CRE :Nfix fl/fl MPs was not impaired compared to control cells.…”

Section: Discussioncontrasting

confidence: 44%

The Transcription Factor Nfix Requires RhoA-ROCK1 Dependent Phagocytosis to Mediate Macrophage Skewing during Skeletal Muscle Regeneration

Saclier

Lapi

Bonfanti

et al. 2020

Cells

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Macrophages (MPs) are immune cells which are crucial for tissue repair. In skeletal muscle regeneration, pro-inflammatory cells first infiltrate to promote myogenic cell proliferation, then they switch into an anti-inflammatory phenotype to sustain myogenic cells differentiation and myofiber formation. This phenotypical switch is induced by dead cell phagocytosis. We previously demonstrated that the transcription factor Nfix, a member of the nuclear factor I (Nfi) family, plays a pivotal role during muscle development, regeneration and in the progression of muscular dystrophies. Here, we show that Nfix is mainly expressed by anti-inflammatory macrophages. Upon acute injury, mice deleted for Nfix in myeloid line displayed a significant defect in the process of muscle regeneration. Indeed, Nfix is involved in the macrophage phenotypical switch and macrophages lacking Nfix failed to adopt an anti-inflammatory phenotype and interact with myogenic cells. Moreover, we demonstrated that phagocytosis induced by the inhibition of the RhoA-ROCK1 pathway leads to Nfix expression and, consequently, to acquisition of the anti-inflammatory phenotype. Our study identified Nfix as a link between RhoA-ROCK1-dependent phagocytosis and the MP phenotypical switch, thus establishing a new role for Nfix in macrophage biology for the resolution of inflammation and tissue repair.

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Section: Discussioncontrasting

confidence: 44%

The Transcription Factor Nfix Requires RhoA-ROCK1 Dependent Phagocytosis to Mediate Macrophage Skewing during Skeletal Muscle Regeneration

Saclier

Lapi

Bonfanti

et al. 2020

Cells

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“…Find-Me signal [24,25,36] LysoPC, ATP, P2Y 2 , ApoJ, ApoE4, Fractalkine (CX 3 CL1), S1P Anti-inflammatory and tolerance responses TGF-β, IL-10…”

Section: Steps References Moleculesmentioning

confidence: 99%

“…ACs release "Find-Me" signals that stimulate migration of phagocytes toward them. Moreover, ACs release "Tolerogenic and Keep-Out" signals to keep neutrophils and antigen-presenting cells away [24,25]. After "Find-Me" signaling, the phagocytes identify ACs via "Eat-Me" signals affected through ligands on ACs [14].…”

Section: Introductionmentioning

confidence: 99%

Ca2+ Flux: Searching for a Role in Efferocytosis of Apoptotic Cells in Atherosclerosis

Tajbakhsh

Kovanen

Rezaee

et al. 2019

JCM

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In atherosclerosis, macrophages in the arterial wall ingest plasma lipoprotein-derived lipids and become lipid-filled foam cells with a limited lifespan. Thus, efficient removal of apoptotic foam cells by efferocytic macrophages is vital to preventing the dying foam cells from forming a large necrotic lipid core, which, otherwise, would render the atherosclerotic plaque vulnerable to rupture and would cause clinical complications. Ca 2+ plays a role in macrophage migration, survival, and foam cell generation. Importantly, in efferocytic macrophages, Ca 2+ induces actin polymerization, thereby promoting the formation of a phagocytic cup necessary for efferocytosis. Moreover, in the efferocytic macrophages, Ca 2+ enhances the secretion of anti-inflammatory cytokines. Various Ca 2+ antagonists have been seminal for the demonstration of the role of Ca 2+ in the multiple steps of efferocytosis by macrophages. Moreover, in vitro and in vivo experiments and clinical investigations have revealed the capability of Ca 2+ antagonists in attenuating the development of atherosclerotic plaques by interfering with the deposition of lipids in macrophages and by reducing plaque calcification. However, the regulation of cellular Ca 2+ fluxes in the processes of efferocytic clearance of apoptotic foam cells and in the extracellular calcification in atherosclerosis remains unknown. Here, we attempted to unravel the molecular links between Ca 2+ and efferocytosis in atherosclerosis and to evaluate cellular Ca 2+ fluxes as potential treatment targets in atherosclerotic cardiovascular diseases.

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“…1 The protein network of apoptosis-p53/CEP-1, BH3/EGL-1, Bcl-2/CED-9, Apaf-1/CED-4, and caspases/CED-3-is evolutionarily conserved in humans and Caenorhabditis elegans and tightly regulated during the irreversible induction of cell death. [3][4][5] Notably, the cellular roles of these death-promoting proteases are not exclusive to apoptosis progression, 6 as several recent studies in C. elegans have demonstrated seemingly non-apoptotic roles of caspases/ CED-3. [3][4][5] Notably, the cellular roles of these death-promoting proteases are not exclusive to apoptosis progression, 6 as several recent studies in C. elegans have demonstrated seemingly non-apoptotic roles of caspases/ CED-3.…”

Section: Introductionmentioning

confidence: 99%

Nucleolar control by a non‐apoptotic p53‐caspases‐deubiquitinylase axis promotes resistance to bacterial infection

Chen

Chu

et al. 2019

FASEB j.

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This is an open access article under the terms of the Creat ive Commo ns Attri butio n-NonCo mmercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. AbstractThe nucleolus is best known for its cellular role in regulating ribosome production and growth. More recently, an unanticipated role for the nucleolus in innate immunity has recently emerged whereby downregulation of fibrillarin and nucleolar contraction confers pathogen resistance across taxa. The mechanism of this downregulation, however, remains obscure. Here we report that rather than fibrillarin itself being the proximal factor in this pathway, the key player is a fibrillarin-stabilizing deubiquitinylase USP-33. This was discovered by a candidate-gene search of Caenorhabditis elegans in which CED-3 caspase was revealed to execute targeted cleavage of USP-33, thus destabilizing fibrillarin. We also showed that cep-1 and ced-3 mutant worms altered nucleolar size and decreased antimicrobial peptide gene, spp-1, expression rendering susceptibility to bacterial infection. These phenotypes were reversed by usp-33 knockdown, thus linking the CEP-1-CED-3-USP-33 pathway with nucleolar control and resistance to bacterial infection in worms. Parallel experiments with the human analogs of caspases and USP36 revealed similar roles in coordinating these two processes. In summary, our work outlined a conserved cascade that connects cell death signaling to nucleolar control and innate immune response.

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Engulfment signals and the phagocytic machinery for apoptotic cell clearance

Cited by 127 publications

References 130 publications

The Transcription Factor Nfix Requires RhoA-ROCK1 Dependent Phagocytosis to Mediate Macrophage Skewing during Skeletal Muscle Regeneration

The Transcription Factor Nfix Requires RhoA-ROCK1 Dependent Phagocytosis to Mediate Macrophage Skewing during Skeletal Muscle Regeneration

Ca2+ Flux: Searching for a Role in Efferocytosis of Apoptotic Cells in Atherosclerosis

Nucleolar control by a non‐apoptotic p53‐caspases‐deubiquitinylase axis promotes resistance to bacterial infection

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