scholarly journals Microglia: Same same, but different

2019 ◽  
Vol 216 (10) ◽  
pp. 2223-2225 ◽  
Author(s):  
Katrin Kierdorf ◽  
Marco Prinz
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Social Behavior ◽  
Motor Function ◽  
Colony Stimulating Factor ◽  
The Central Nervous System ◽  
Stimulating Factor

Microglial identity in the central nervous system (CNS) is dependent on colony stimulating factor 1 receptor (CSF-1R) signaling and its ligands IL-34 and colony stimulating factor 1 (CSF-1). In this issue of JEM, Kana et al. (https://doi.org/10.1084/jem.20182037) make the important discovery that CSF-1, but not IL-34, orchestrates cerebellar microglial homeostasis in mice, and its deficiency resulted in severe cerebellar dysfunctions accompanied by defects in motor function and social behavior.

scholarly journals Insights Into the Role of CSF1R in the Central Nervous System and Neurological Disorders

2021 ◽  
Vol 13 ◽  
Author(s):  
Banglian Hu ◽  
Shengshun Duan ◽  
Ziwei Wang ◽  
Xin Li ◽  
Yuhang Zhou ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Neurological Disorders ◽  
Neurological Diseases ◽  
Colony Stimulating Factor ◽  
Loss Of Function ◽  
Axonal Spheroids ◽  
The Central Nervous System ◽  
Stimulating Factor

The colony-stimulating factor 1 receptor (CSF1R) is a key tyrosine kinase transmembrane receptor modulating microglial homeostasis, neurogenesis, and neuronal survival in the central nervous system (CNS). CSF1R, which can be proteolytically cleaved into a soluble ectodomain and an intracellular protein fragment, supports the survival of myeloid cells upon activation by two ligands, colony stimulating factor 1 and interleukin 34. CSF1R loss-of-function mutations are the major cause of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) and its dysfunction has also been implicated in other neurodegenerative disorders including Alzheimer’s disease (AD). Here, we review the physiological functions of CSF1R in the CNS and its pathological effects in neurological disorders including ALSP, AD, frontotemporal dementia and multiple sclerosis. Understanding the pathophysiology of CSF1R is critical for developing targeted therapies for related neurological diseases.

scholarly journals Permanent neuroglial remodeling of the retina following infiltration of CSF1R inhibition-resistant peripheral monocytes

2018 ◽  
Vol 115 (48) ◽  
pp. E11359-E11368 ◽  
Author(s):  
Eleftherios I. Paschalis ◽  
Fengyang Lei ◽  
Chengxin Zhou ◽  
Vassiliki Kapoulea ◽  
Reza Dana ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Bone Marrow ◽  
Nervous System ◽  
Ocular Injury ◽  
Colony Stimulating Factor ◽  
Mhc Ii ◽  
Tnf Α ◽  
The Central Nervous System ◽  
Stimulating Factor

Previous studies have demonstrated that ocular injury can lead to prompt infiltration of bone-marrow–derived peripheral monocytes into the retina. However, the ability of these cells to integrate into the tissue and become microglia has not been investigated. Here we show that such peripheral monocytes that infiltrate into the retina after ocular injury engraft permanently, migrate to the three distinct microglia strata, and adopt a microglia-like morphology. In the absence of ocular injury, peripheral monocytes that repopulate the retina after depletion with colony-stimulating factor 1 receptor (CSF1R) inhibitor remain sensitive to CSF1R inhibition and can be redepleted. Strikingly, consequent to ocular injury, the engrafted peripheral monocytes are resistant to depletion by CSF1R inhibitor and likely express low CSF1R. Moreover, these engrafted monocytes remain proinflammatory, expressing high levels of MHC-II, IL-1β, and TNF-α over the long term. The observed permanent neuroglia remodeling after injury constitutes a major immunological change that may contribute to progressive retinal degeneration. These findings may also be relevant to other degenerative conditions of the retina and the central nervous system.

scholarly journals A csf1rb mutation uncouples two waves of microglia development in zebrafish

Development ◽  
2020 ◽  
pp. dev.194241
Author(s):  
Giuliano Ferrero ◽  
Magali Miserocchi ◽  
Elodie Di Ruggiero ◽  
Valérie Wittamer
Keyword(s):  
Central Nervous System ◽  
Adult Population ◽  
Colony Stimulating Factor ◽  
Hematopoietic Stem ◽  
Mapping Strategy ◽  
The Central Nervous System ◽  
Evolutionary Aspects ◽  
Stimulating Factor ◽  
Specific Contribution

In vertebrates, the ontogeny of microglia, the resident macrophages of the central nervous system, initiates early during development from primitive macrophages. While murine embryonic microglia then persist through life, in zebrafish these cells are transient, as they are fully replaced by an adult population originating from larval hematopoietic stem cell (HSC)-derived progenitors. Colony-stimulating factor receptor 1 (csf1r) is a fundamental regulator of microglia ontogeny in vertebrates, including zebrafish which possess two paralogous genes: csf1ra and csf1rb. While previous work showed mutation in both genes completely abrogates microglia development, the specific contribution of each paralog remains largely unknown. Here, using a fate-mapping strategy to discriminate between the two microglial waves, we uncover non-overlapping roles for csf1ra and csf1rb in hematopoiesis, and identified csf1rb as an essential regulator of adult microglia development. Notably, we demonstrate that csf1rb positively regulates HSC-derived myelopoiesis, resulting in macrophage deficiency, including microglia, in adult mutant animals. Overall, this study contributes to new insights into evolutionary aspects of Csf1r signaling and provides an unprecedented framework for the functional dissection of embryonic versus adult microglia in vivo.

scholarly journals Circulating Ly-6C+ myeloid precursors migrate to the CNS and play a pathogenic role during autoimmune demyelinating disease

Blood ◽  
2009 ◽  
Vol 113 (14) ◽  
pp. 3190-3197 ◽  
Author(s):  
Irah L. King ◽  
Travis L. Dickendesher ◽  
Benjamin M. Segal
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Dendritic Cells ◽  
Demyelinating Disease ◽  
Colony Stimulating Factor ◽  
Prominent Component ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Autoimmune Demyelination ◽  
Stimulating Factor

Abstract Mature myeloid cells (macrophages and CD11b+ dendritic cells) form a prominent component of neuroinflammatory infiltrates in multiple sclerosis and experimental autoimmune encephalomyelitis (EAE). The mechanism by which these cells are replenished during relapsing and chronic neuroinflammation is poorly understood. Here we demonstrate that CD11b+CD62L+Ly6Chi monocytes with colony-forming potential are mobilized into the bloodstream by a granulocyte-macrophage colony-stimulating factor-dependent pathway immediately before EAE relapses. Circulating Ly6Chi monocytes traffic across the blood-brain barrier, up-regulate proinflammatory molecules, and differentiate into central nervous system dendritic cells and macrophages. Enrichment of Ly6Chi monocytes in the circulating pool is associated with an earlier onset and increased severity of clinical EAE. Our studies indicate that granulocyte-macrophage colony-stimulating factor–driven release of Ly6Chi precursors from the bone marrow prevents exhaustion of central nervous system myeloid populations during relapsing or chronic autoimmune demyelination, suggesting a novel pathway for therapeutic targeting.

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