Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Astrocyte-derived Interleukin-33 promotes microglial synapse engulfment and neural circuit development I

ABSTRACT: Neuronal synapse formation and remodeling is essential to central nervous system (CNS) development and is dysfunctional in neurodevelopmental diseases. Innate immune signals regulate tissue remodeling in the periphery, but how this impacts CNS synapses is largely unknown. Here we show that the IL-1 family cytokine Interleukin-33 (IL-33) is produced by developing astrocytes and is developmentally required for normal synapse numbers and neural circuit function in the spinal cord and thalamus. We find that IL-33 signals primarily to microglia under physiologic conditions, that it promotes microglial synapse engulfment, and that it can drive microglial-dependent synapse depletion in vivo. These data reveal a cytokine-mediated mechanism required to maintain synapse homeostasis during CNS development.

ORGANISM(S): Mus musculus

PROVIDER: GSE109352 | GEO | 2018/02/05

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Astrocyte-derived Interleukin-33 promotes microglial synapse engulfment and neural circuit development II

Project description:Neuronal synapse formation and remodeling is essential to central nervous system (CNS) development and is dysfunctional in neurodevelopmental diseases. Innate immune signals regulate tissue remodeling in the periphery, but how this impacts CNS synapses is largely unknown. Here we show that the IL-1 family cytokine Interleukin-33 (IL-33) is produced by developing astrocytes and is developmentally required for normal synapse numbers and neural circuit function in the spinal cord and thalamus. We find that IL-33 signals primarily to microglia under physiologic conditions, that it promotes microglial synapse engulfment, and that it can drive microglial-dependent synapse depletion in vivo. These data reveal a cytokine-mediated mechanism required to maintain synapse homeostasis during CNS development.

2018-02-05 | GSE109353 | GEO

Astrocyte-derived Interleukin-33 promotes microglial synapse engulfment and neural circuit development

Project description:Astrocyte-derived Interleukin-33 promotes microglial synapse engulfment and neural circuit development

| PRJNA430536 | ENA

Astrocyte-derived Interleukin-33 promotes microglial synapse engulfment and neural circuit development I

Project description:Astrocyte-derived Interleukin-33 promotes microglial synapse engulfment and neural circuit development I

| PRJNA430779 | ENA

Astrocyte-derived Interleukin-33 promotes microglial synapse engulfment and neural circuit development II

Project description:Astrocyte-derived Interleukin-33 promotes microglial synapse engulfment and neural circuit development II

| PRJNA430778 | ENA

Essential omega-3 fatty acids tune microglial phagocytosis of synaptic elements in the developing brain

Project description:<p>Omega-3 fatty acids (n-3 polyunsaturated fatty acids; n-3 PUFAs) are essential for the functional maturation of the brain. Westernization of dietary habits in both developed and developing countries is accompanied by a progressive reduction in dietary intake of n-3 PUFAs. Low maternal intake of n-3 PUFAs has been linked to neurodevelopmental diseases in epidemiological studies, but the mechanisms by which a n-3 PUFA dietary imbalance affects CNS development are poorly understood. Active microglial engulfment of synaptic elements is an important process for normal brain development and altered synapse refinement is a hallmark of several neurodevelopmental disorders. Here, we identify a molecular mechanism for detrimental effects of low maternal n-3 PUFA intake on hippocampal development. Our results show that maternal dietary n-3 PUFA deficiency increases microglial phagocytosis of synaptic elements in the developing hippocampus, partly through the activation of 12/15- lipoxygenase (LOX)/12-HETE signaling, which alters neuronal morphology and affects cognition in the postnatal offspring. While women of child bearing age are at higher risk of dietary n-3 PUFA deficiency, these findings provide new insights into the mechanisms linking maternal nutrition to neurodevelopmental disorders.</p>

2020-11-03 | MTBLS1952 | MetaboLights

IL-33-PU.1 transcriptome reprogramming drives functional state transition and clearance activity of microglia in Alzheimer’s disease

Project description:Impairment of microglial clearance activity contributes to beta-amyloid (Aβ) pathology in Alzheimer disease (AD). While the transcriptome profile of microglia directs microglial functions, how the microglial transcriptome can be regulated to alleviate AD pathology is largely unknown. Here, we show that injection of interleukin (IL)-33 in an AD transgenic mouse model ameliorates Aβ pathology by reprogramming microglial epigenetic and transcriptomic profiles to induce a microglial subpopulation with enhanced phagocytic activity. These IL-33–responsive microglia (IL-33RM) express distinct transcriptome signature, highlighted by major histocompatibility complex class II genes, and restored homeostatic signature genes. IL-33–induced remodeling of chromatin accessibility and PU.1 transcription factor binding at the signature genes of IL-33RM control their transcriptome reprogramming. Specifically, disrupting PU.1–DNA interaction abolishes the microglial state transition and Aβ clearance induced by IL-33. Thus, we define a PU.1-dependent transcriptional pathway that drives the IL-33–induced functional state transition of microglia, resulting in enhanced Aβ clearance.

2020-05-01 | GSE147495 | GEO

The VCAM1–ApoE pathway directs microglial chemotaxis and alleviates Alzheimer’s disease pathology

Project description:In Alzheimer’s disease (AD), sensome receptor dysfunction impairs microglial danger-associated molecular pattern (DAMP) clearance and exacerbates disease pathology. While extrinsic signals including interleukin-33 (IL-33) can restore microglial DAMP clearance, it remains largely unclear how the sensome receptor(s) is regulated and interacts with DAMP during phagocytic clearance. Here, we show that IL-33 induces VCAM1 in microglia, which promotes microglial chemotaxis toward amyloid-beta (Aβ) plaque-associated ApoE, and leads to Aβ clearance. We show that IL-33 stimulates a chemotactic state in microglia, characterized by Aβ-directed migration. Functional screening identified that VCAM1 directs microglial Aβ chemotaxis by sensing Aβ plaque-associated ApoE. Moreover, we found that disrupting VCAM1–ApoE interaction abolishes microglial Aβ chemotaxis, resulting in decreased microglial clearance of Aβ. In patients with AD, higher cerebrospinal fluid levels of soluble VCAM1 were correlated with impaired microglial Aβ chemotaxis. Together, our findings demonstrate that promoting VCAM1–ApoE-dependent microglial functions ameliorates AD pathology.

2023-07-18 | GSE208006 | GEO

Early life inflammation promotes depressive symptoms in adolescents via microglial engulfment of dendritic spines

Project description:Early life inflammation is known to promote the risk of depression in later life. Here, we demonstrate how early life inflammation causes adolescent depressive-like symptoms: by altering the long-term neuronal spine engulfment capacity of microglia. For mice exposed to lipopolysaccharide (LPS)-induced inflammation via the Toll-like receptor 4/NF-κB signaling pathway at postnatal day 14 (P14), ongoing longitudinal imaging of the living brain revealed that later stress (delivered during adolescence on P45) increases the extent of microglial engulfment around anterior cingulate cortex (ACC) glutamatergic neuronal (ACCGlu) spines. Through bluk RNA-seq of ACC tissue, we find that the fractalkine receptor CX3CR1 mediates stress-induced engulfment of ACCGlu neuronal spines.

2021-06-04 | GSE176140 | GEO

Bulk RNA-seq of FACS sorted astrocytes upon microglial depletion

Project description:As the professional phagocyte in the central nervous system (CNS), microglia are the primary scavenger removing cell corpses. The failure of microglia in debris clearance influences the normal CNS function. Meanwhile, microglia undergo turnover during the whole lifespan. If dead microglia are not timely removed, accumulated corpses may influence the CNS function. The microglial corpse clearance is hereby crucial for CNS homeostasis. However, the underlying mechanism remains obscure. In this study, we investigated how microglial corpses are removed. We found that microglial corpses are mainly phagocytosed by astrocytes, mediated by C4b opsonization. Then engulfed microglial fragments are degraded in astrocytes via the RUBICON-dependent LC3-associated phagocytosis (LAP), a form of non-canonical autophagy. The interference of the C4b-mediated engulfment and its subsequent LAP disrupt the microglial debris removal and degradation, respectively. Together, we elucidated cellular and molecular mechanisms of microglial debris removal, extending the knowledge on how the CNS homeostasis is maintained.

2022-09-01 | GSE171321 | GEO

Mass spectrometry analysis of cleavage sites for different protease allergens in human IL-33

Project description:The cytokine interleukin-33 (IL-33) is an epithelial alarmin with critical roles in allergic inflammation and type 2 immunity. The project aims at the characterization of the direct cleavage of IL-33 by allergen proteases, resulting in its activation, and in the subsequent induction of type 2 cytokine production in group 2 innate lymphoid cells. The present dataset contains mass spectrometry analyses to map the cleavage sites for 9 distinct allergens proteases in the human IL-33 sequence.

2018-03-14 | PXD006081 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data