Living on the Edge: Efferocytosis at the Interface of Homeostasis and Pathology

Morioka, Sho; Maueröder, Christian; Ravichandran, Kodi S.

doi:10.1016/j.immuni.2019.04.018

Cited by 265 publications

(292 citation statements)

References 160 publications

(154 reference statements)

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“…In the brain, microglia remove the excess newborn cells produced during embryonic and postnatal development in the cortex, cerebellum and amygdala (62)(63)(64) and in adult neurogenic niches in the hippocampus and subventricular zone (SVZ) (37, 65), as well as deceased cells during aging and neurodegenerative diseases (66). Other cell types, such as astrocytes, neuroblasts or cells of the neural crest may also act as phagocytes but generally with less efficiency and thus microglia are considered the brain "professional" phagocytes (67).…”

Section: Phagocytosis By Macrophages and Microgliamentioning

confidence: 99%

“…Phagocytosis and apoptosis are evolutionarily linked together as a mechanism that allows the elimination of excess, dysfunctional, or aged cells without imposing alterations or damage in the surrounding cells (67). Homeostatic phagocytosis is ensured by the immediate recognition of the apoptotic cell by phagocytes through a redundant plethora of released "find-me" and membrane-bound "eat-me" signals that are recognized by the phagocytes ( Table 1).…”

Section: Lesson 6 Phagocytosis Is Tightly Coupled To Apoptosis Due Tmentioning

confidence: 99%

“…Homeostatic phagocytosis is ensured by the immediate recognition of the apoptotic cell by phagocytes through a redundant plethora of released "find-me" and membrane-bound "eat-me" signals that are recognized by the phagocytes ( Table 1). Herein we summarize some of the most relevant signals and receptors involved in apoptotic cell recognition, and we prompt the reader to comprehensive reviews on the topic for more details (67,72).…”

Section: Lesson 6 Phagocytosis Is Tightly Coupled To Apoptosis Due Tmentioning

confidence: 99%

“…And the beta glucan receptor Clec7a, associated to the phagocytosis of oligodendrocytes by microglia during early postnatal development (48). Each type of phagocyte expresses their own set of receptors (67) and microglia is no exception. The most conspicuous phagocytosis receptors expressed in both mouse and human microglia are CX3CR1, P2Y6, P2Y12, stabilin 1, SIRPα, TREM2, MerTK, and CD11b, based on brain RNASeq databases (68,69) and the immunological RNASeq database Skyline (http://rstats.immgen.org/Skyline/skyline.html) ( Table 1).…”

Section: Lesson 6 Phagocytosis Is Tightly Coupled To Apoptosis Due Tmentioning

confidence: 99%

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Microglial Corpse Clearance: Lessons From Macrophages

et al. 2020

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From development to aging and disease, the brain parenchyma is under the constant threat of debris accumulation, in the form of dead cells and protein aggregates. To prevent garbage buildup, the brain is equipped with efficient phagocytes: the microglia. Microglia are similar, but not identical to other tissue macrophages, and in this review, we will first summarize the differences in the origin, lineage and population maintenance of microglia and macrophages. Then, we will discuss several principles that govern macrophage phagocytosis of apoptotic cells (efferocytosis), including the existence of redundant recognition mechanisms ("find-me" and "eat-me") that lead to a tight coupling between apoptosis and phagocytosis. We will then describe that resulting from engulfment and degradation of apoptotic cargo, phagocytes undergo an epigenetic, transcriptional and metabolic rewiring that leads to trained immunity, and discuss its relevance for microglia and brain function. In summary, we will show that neuroimmunologists can learn many lessons from the well-developed field of macrophage phagocytosis biology.

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Section: Phagocytosis By Macrophages and Microgliamentioning

confidence: 99%

Section: Lesson 6 Phagocytosis Is Tightly Coupled To Apoptosis Due Tmentioning

confidence: 99%

Section: Lesson 6 Phagocytosis Is Tightly Coupled To Apoptosis Due Tmentioning

confidence: 99%

Section: Lesson 6 Phagocytosis Is Tightly Coupled To Apoptosis Due Tmentioning

confidence: 99%

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Microglial Corpse Clearance: Lessons From Macrophages

et al. 2020

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“…During efferocytosis, phagocytic cells recognize membrane-associated or soluble "eat-me" signals on dying cells. Thereafter, the phagocyte engulfs the apoptotic cell, and thereby prevents the exposure of the surrounding tissue to harmful intracellular components [1][2][3].…”

Section: Introductionmentioning

confidence: 99%

Myeloid SOCS3 Deficiency Regulates Angiogenesis via Enhanced Apoptotic Endothelial Cell Engulfment

et al. 2019

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Mononuclear phagocytes, such as macrophages and microglia, are key regulators of organ homeostasis including vascularization processes. Here, we investigated the role of the suppressor of cytokine signaling 3 (SOCS3) in myeloid cells as a regulator of mononuclear phagocyte function and their interaction with endothelial cells in the context of sprouting angiogenesis. As compared to SOCS3-sufficient counterparts, SOCS3-deficient microglia and macrophages displayed an increased phagocytic activity toward primary apoptotic endothelial cells, which was associated with an enhanced expression of the opsonin growth arrest-specific 6 (Gas6), a major prophagocytic molecule. Furthermore, we found that myeloid SOCS3 deficiency significantly reduced angiogenesis in an ex vivo mouse aortic ring assay, which could be reversed by the inhibition of the Gas6 receptor Mer. Together, SOCS3 in myeloid cells regulates the Gas6/Merdependent phagocytosis of endothelial cells, and thereby angiogenesis-related processes. Our findings provide novel insights into the complex crosstalk between mononuclear phagocytes and endothelial cells, and may therefore provide a new platform for the development of new antiangiogenic therapies.

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Promoting Diabetic Wound Healing through a Hydrogel‐Based Cascade Regulation Strategy of Fibroblast‐Macrophage

Jin,

Wang,

Tang

et al. 2024

Adv Healthcare Materials

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The management of diabetic wounds (DWs) continues to pose a significant challenge in the field of medicine. DWs are primarily prevented from healing due to damage to macrophage efferocytosis and fibroblast dysfunction. Consequently, treatment strategy that involve both immunoregulation and the promotion of extracellular matrix (ECM) formation hold promise for healing DWs. Nevertheless, existing treatment methods necessitate complex interventions and are associated with increased costs, for example, the use of cytokines and cell therapy, both of which have limited effectiveness. In this study, a new type of ruthenium (IV) oxide nanoparticles (RNPs)‐laden hybrid hydrogel dressing with a double network of Pluronic F127 and F68 has been developed. Notably, the hybrid hydrogel demonstrates remarkable thermosensitivity, injectability, immunoregulatory characteristics and healing capability. RNPs in hydrogel effectively regulate both fibroblasts and macrophages in a cascade manner, stimulating fibroblast differentiation while synergistically enhancing the efferocytosis of macrophage. The immunoregulatory character of the hydrogel aids in restoring the intrinsic stability of the immune microenvironment in the wound and facilitates essential remodeling of the ECM. This hydrogel therefore offers a novel approach for treating DWs through intercellular communication.This article is protected by copyright. All rights reserved

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Living on the Edge: Efferocytosis at the Interface of Homeostasis and Pathology

Cited by 265 publications

References 160 publications

Microglial Corpse Clearance: Lessons From Macrophages

Microglial Corpse Clearance: Lessons From Macrophages

Myeloid SOCS3 Deficiency Regulates Angiogenesis via Enhanced Apoptotic Endothelial Cell Engulfment

Promoting Diabetic Wound Healing through a Hydrogel‐Based Cascade Regulation Strategy of Fibroblast‐Macrophage

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