Microglia Biology: One Century of Evolving Concepts

Cell, Journal Year: 2019, Volume and Issue: 179(2), P. 292 - 311

Published: Oct. 1, 2019

Language: Английский

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Phagocytosis checkpoints as new targets for cancer immunotherapy

Nature reviews. Cancer, Journal Year: 2019, Volume and Issue: 19(10), P. 568 - 586

Published: Aug. 28, 2019

Language: Английский

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The CD47-SIRPα Immune Checkpoint

Immunity, Journal Year: 2020, Volume and Issue: 52(5), P. 742 - 752

Published: May 1, 2020

Language: Английский

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Microglia: Immune and non-immune functions

Immunity, Journal Year: 2021, Volume and Issue: 54(10), P. 2194 - 2208

Published: Oct. 1, 2021

Language: Английский

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Type I interferon response drives neuroinflammation and synapse loss in Alzheimer disease

Journal of Clinical Investigation, Journal Year: 2020, Volume and Issue: 130(4), P. 1912 - 1930

Published: Jan. 9, 2020

Type I interferon (IFN) is a key cytokine that curbs viral infection and cell malignancy. Previously, we demonstrated potent IFN immunogenicity of nucleic acid–containing (NA-containing) amyloid fibrils in the periphery. Here, investigated whether associated with β-amyloidosis inside brain contributes to neuropathology. An IFN-stimulated gene (ISG) signature was detected brains multiple murine Alzheimer disease (AD) models, phenomenon also observed WT mouse challenged generic NA-containing fibrils. In vitro, microglia innately responded AD activated ISG-expressing exclusively surrounded NA+ β plaques, which accumulated an age-dependent manner. Brain administration rIFN-β resulted microglial activation complement C3-dependent synapse elimination vivo. Conversely, selective receptor blockade effectively diminished ongoing microgliosis loss models. Moreover, enveloping neuritic plaques postmortem patients AD. Gene expression interrogation revealed pathway grossly upregulated clinical significantly correlated severity activation. Therefore, constitutes pivotal element within neuroinflammatory network critically neuropathogenic processes.

Language: Английский

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How macrophages deal with death

Nature reviews. Immunology, Journal Year: 2019, Volume and Issue: 19(9), P. 539 - 549

Published: April 24, 2019

Language: Английский

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Local externalization of phosphatidylserine mediates developmental synaptic pruning by microglia

The EMBO Journal, Journal Year: 2020, Volume and Issue: 39(16)

Published: July 13, 2020

Neuronal circuit assembly requires the fine balance between synapse formation and elimination. Microglia, through elimination of supernumerary synapses, have an established role in this process. While microglial receptor TREM2 soluble complement proteins C1q C3 are recognized as key players, neuronal molecular components that specify synapses to be eliminated still undefined. Here, we show exposed phosphatidylserine (PS) represents a "eat-me" signal involved microglial-mediated pruning. In hippocampal neuron microglia co-cultures, can partially prevented by blocking accessibility PS using Annexin V or loss TREM2. vivo, exposure at both retinogeniculate engulfment PS-labeled material occurs during developmental periods Mice deficient C1q, which fail properly refine connections, elevated presynaptic reduced microglia. These data provide mechanistic insight into pruning identify novel developmentally regulated is common among developing brain structures.

Language: Английский

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Microglia regulation of synaptic plasticity and learning and memory

Neural Regeneration Research, Journal Year: 2021, Volume and Issue: 17(4), P. 705 - 705

Published: Aug. 29, 2021

Microglia are the resident macrophages of central nervous system. possess varied morphologies and functions. Under normal physiological conditions, microglia mainly exist in a resting state constantly monitor their microenvironment survey neuronal synaptic activity. Through C1q, C3 CR3 "Eat Me" CD47 SIRPα "Don't Eat complement pathways, as well other pathways such CX3CR1 signaling, regulate pruning, process crucial for promotion synapse formation regulation activity plasticity. By mediating play an important role experience-dependent plasticity barrel cortex visual after whisker removal or monocular deprivation, also learning memory, including modulation memory strength, forgetfulness, quality. As response to brain injury, infection neuroinflammation, become activated increase number. Activated change amoeboid shape, migrate sites inflammation secrete proteins cytokines, chemokines reactive oxygen species. These molecules released by can lead deficits associated with aging, Alzheimer's disease, traumatic HIV-associated neurocognitive disorder, neurological mental disorders autism, depression post-traumatic stress disorder. With focus on recently published literature, here we reviewed studies investigating how modulate disease-related deficits. summarizing function these processes, aim provide overview discuss possibility manipulation therapeutic ameliorate cognitive disorders.

Language: Английский

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Neuron-Glia Signaling in Synapse Elimination

Annual Review of Neuroscience, Journal Year: 2019, Volume and Issue: 42(1), P. 107 - 127

Published: July 8, 2019

Maturation of neuronal circuits requires selective elimination synaptic connections. Although neuron-intrinsic mechanisms are important in this process, it is increasingly recognized that glial cells also play a critical role. Without proper functioning these cells, the number, morphology, and function contacts profoundly altered, resulting abnormal connectivity behavioral abnormalities. In addition to their role refinement, have been implicated pathological synapse loss dysfunction following injury or nervous system degeneration adults. regulating glia-mediated still being uncovered, clear complex process involves many cues promote inhibit removal specific Gaining greater understanding signals contribution different cell types will not only provide insight into biological event but be instrumental advancing knowledge brain development neural disease.

Language: Английский

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Mechanisms governing activity-dependent synaptic pruning in the developing mammalian CNS

Nature reviews. Neuroscience, Journal Year: 2021, Volume and Issue: 22(11), P. 657 - 673

Published: Sept. 20, 2021

Language: Английский

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