Astrocytic phagocytosis is a compensatory mechanism for microglial dysfunction

Konishi, Hiroyuki; Okamoto, Takayuki; Hara, Yuichiro; Komine, Okiru; Tamada, Hiromi; Maeda, Masayuki; Osako, Fumika; Kobayashi, Masaaki; Nishiyama, Akira; Kataoka, Yosky; Takai, Toshiyuki; Udagawa, Nobuyuki; Jung, Steffen; Ozato, Keiko; Tamura, Tomohide; Tsuda, Makoto; Yamanaka, Koji; Ogi, Tomoo; Sato, Katsuaki; Kiyama, Hiroshi

doi:10.15252/embj.2020104464

Cited by 124 publications

(135 citation statements)

References 73 publications

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“…Interestingly, epithelial cells are also related to the potential epithelial origin of some EMP progenitors (Plein et al, 2018 ). Because microglia are macrophage-related cells of the central nervous system and originated from embryonic EMPs (Konishi et al, 2020 ), the majority of postnatal brain microglia expressed eYFP in Rank-Cre; Rosa26eYFP mice. It is well-recognized that RANK is the receptor for RANKL and RANK-RANKL signaling essential for osteoclast differentiation and activation.…”

Section: Unique Expression Profiles Of Emps- and Hscs-derived Macrophmentioning

confidence: 99%

Monocyte/Macrophage Lineage Cells From Fetal Erythromyeloid Progenitors Orchestrate Bone Remodeling and Repair

Yahara

Gracia

et al. 2021

Front. Cell Dev. Biol.

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A third of the population sustains a bone fracture, and the pace of fracture healing slows with age. The slower pace of repair is responsible for the increased morbidity in older individuals who sustain a fracture. Bone healing progresses through overlapping phases, initiated by cells of the monocyte/macrophage lineage. The repair process ends with remodeling. This last phase is controlled by osteoclasts, which are bone-specific multinucleated cells also of the monocyte/macrophage lineage. The slower rate of healing in aging can be rejuvenated by macrophages from young animals, and secreted proteins from macrophage regulate undifferentiated mesenchymal cells to become bone-forming osteoblasts. Macrophages can derive from fetal erythromyeloid progenitors or from adult hematopoietic progenitors. Recent studies show that fetal erythromyeloid progenitors are responsible for the osteoclasts that form the space in bone for hematopoiesis and the fetal osteoclast precursors reside in the spleen postnatally, traveling through the blood to participate in fracture repair. Differences in secreted proteins between macrophages from old and young animals regulate the efficiency of osteoblast differentiation from undifferentiated mesenchymal precursor cells. Interestingly, during the remodeling phase osteoclasts can form from the fusion between monocyte/macrophage lineage cells from the fetal and postnatal precursor populations. Data from single cell RNA sequencing identifies specific markers for populations derived from the different precursor populations, a finding that can be used in future studies. Here, we review the diversity of macrophages and osteoclasts, and discuss recent finding about their developmental origin and functions, which provides novel insights into their roles in bone homeostasis and repair.

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Section: Unique Expression Profiles Of Emps- and Hscs-derived Macrophmentioning

confidence: 99%

Monocyte/Macrophage Lineage Cells From Fetal Erythromyeloid Progenitors Orchestrate Bone Remodeling and Repair

Yahara

Gracia

et al. 2021

Front. Cell Dev. Biol.

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“…Complement-3 receptor (CR3), Mac-2 (Glactin-3), CD36, scavenger receptor AI/II (SRAI/II), and triggering receptor expressed on myeloid cells 2 (TREM2) have been proposed as receptors for myelin debris phagocytosis by Mφ and microglia (Kuhlmann et al, 2002;Napoli and Neumann, 2010;Sun et al, 2010;Zhou et al, 2014;Wang et al, 2015;Kopper and Gensel, 2018). The semiprofessional phagocytes, such as astrocytes and endothelial cells, can engulf myelin debris as well (Zhou et al, 2019;Konishi et al, 2020;Wang et al, 2020). We recently demonstrated that newly formed microvessels and lining microvascular endothelial cells in the injured spinal cord can engulf IgG-opsonized myelin debris (Zhou et al, 2019).…”

Section: Phagocytosis Of Cell Debrismentioning

confidence: 99%

For Better or for Worse: A Look Into Neutrophils in Traumatic Spinal Cord Injury

Zivkovic

Ayazi

Hammel

et al. 2021

Front. Cell. Neurosci.

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Neutrophils are short-lived cells of the innate immune system and the first line of defense at the site of an infection and tissue injury. Pattern recognition receptors on neutrophils recognize pathogen-associated molecular patterns or danger-associated molecular patterns, which recruit them to the destined site. Neutrophils are professional phagocytes with efficient granular constituents that aid in the neutralization of pathogens. In addition to phagocytosis and degranulation, neutrophils are proficient in creating neutrophil extracellular traps (NETs) that immobilize pathogens to prevent their spread. Because of the cytotoxicity of the associated granular proteins within NETs, the microbes can be directly killed once immobilized by the NETs. The role of neutrophils in infection is well studied; however, there is less emphasis placed on the role of neutrophils in tissue injury, such as traumatic spinal cord injury. Upon the initial mechanical injury, the innate immune system is activated in response to the molecules produced by the resident cells of the injured spinal cord initiating the inflammatory cascade. This review provides an overview of the essential role of neutrophils and explores the contribution of neutrophils to the pathologic changes in the injured spinal cord.

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“…Correlative light and electron microscopy (CLEM) has brought minimally invasive optical in vivo imaging (usually fluorescence) together with the nanometer resolution of serial section TEM (Transmission Electron Microscopy) or similar EM techniques. A large amount of information about structures and dynamics of the neuroimmune cells can be obtained from the same sample [ 177 , 178 ]. Weinhard and coworkers used CLEM to perform a 3D ultrastructural characterization of organotypic hippocampal cultures, enriching the understanding of the dynamic interaction of postsynaptic spines with microglia [ 179 ].…”

Section: Studying Microglia–neuron Crosstalk With Advanced Microscmentioning

confidence: 99%

Epigenetics and Communication Mechanisms in Microglia Activation with a View on Technological Approaches

et al. 2021

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Microglial cells, the immune cells of the central nervous system (CNS), play a crucial role for the proper brain development and function and in CNS homeostasis. While in physiological conditions, microglia continuously check the state of brain parenchyma, in pathological conditions, microglia can show different activated phenotypes: In the early phases, microglia acquire the M2 phenotype, increasing phagocytosis and releasing neurotrophic and neuroprotective factors. In advanced phases, they acquire the M1 phenotype, becoming neurotoxic and contributing to neurodegeneration. Underlying this phenotypic change, there is a switch in the expression of specific microglial genes, in turn modulated by epigenetic changes, such as DNA methylation, histones post-translational modifications and activity of miRNAs. New roles are attributed to microglial cells, including specific communication with neurons, both through direct cell–cell contact and by release of many different molecules, either directly or indirectly, through extracellular vesicles. In this review, recent findings on the bidirectional interaction between neurons and microglia, in both physiological and pathological conditions, are highlighted, with a focus on the complex field of microglia immunomodulation through epigenetic mechanisms and/or released factors. In addition, advanced technologies used to study these mechanisms, such as microfluidic, 3D culture and in vivo imaging, are presented.

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Astrocytic phagocytosis is a compensatory mechanism for microglial dysfunction

Cited by 124 publications

References 73 publications

Monocyte/Macrophage Lineage Cells From Fetal Erythromyeloid Progenitors Orchestrate Bone Remodeling and Repair

Monocyte/Macrophage Lineage Cells From Fetal Erythromyeloid Progenitors Orchestrate Bone Remodeling and Repair

For Better or for Worse: A Look Into Neutrophils in Traumatic Spinal Cord Injury

Epigenetics and Communication Mechanisms in Microglia Activation with a View on Technological Approaches

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