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Cited by 98Neuroinflammation and Neurodegeneration MechanismsTryptophan and brain disordersInflammasome and immune disorders

Decreased neuronal CD200 expression in IL-4-deficient mice results in increased neuroinflammation in response to lipopolysaccharide

Lyons, Anthony, McQuillan, Keith, Deighan, Brian F., O’Reilly, Julie-Ann, Downer, Eric J., Murphy, Aine C., Watson, Melanie, Piazza, Alessia +4 more·2009·Brain, Behavior, and Immunity
DOI 10.1016/j.bbi.2009.05.060
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Abstract

Maintenance of the balance between pro- and anti-inflammatory cytokines in the brain, which is affected by the activation state of microglia, is important for maintenance of neuronal function. Evidence has suggested that IL-4 plays an important neuromodulatory role and has the ability to decrease lipopolysaccharide-induced microglial activation and the production of IL-1beta. We have also demonstrated that CD200-CD200R interaction is involved in immune homeostasis in the brain. Here, we investigated the anti-inflammatory role of IL-4 and, using in vitro and in vivo analysis, established that the effect of lipopolysaccharide was more profound in IL-4(-/-), compared with wildtype, mice. Intraperitoneal injection of lipopolysaccharide exerted a greater inhibitory effect on exploratory behaviour in IL-4(-/-), compared with wildtype, mice and this was associated with evidence of microglial activation. We demonstrate that the increase in microglial activation is inversely related to CD200 expression. Furthermore, CD200 was decreased in neurons prepared from IL-4(-/-) mice, whereas stimulation with IL-4 enhanced CD200 expression. Importantly, neurons prepared from wildtype, but not from IL-4(-/-), mice attenuated the lipopolysaccharide-induced increase in pro-inflammatory cytokine production by glia. These findings suggest that the neuromodulatory effect of IL-4, and in particular its capacity to maintain microglia in a quiescent state, may result from its ability to upregulate CD200 expression on neurons.

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  • The heightened inflammatory profile in IL-4 knockout mice is associated with exacerbated sickness behavior, lack of social exploration, and enhanced anxiety-like behavior.

    “Furthermore, this heightened inflammatory profile was associated with exacerbated sickness behavior, lack of social exploration, and enhanced anxiety-like behavior (Lyons et al, 2009).”

    From Microglia Priming with Aging and Stress (2017) · cites this paper as Lyons et al, 2009

  • IL-4 knockout mice have reduced baseline expression of CD200 at mRNA and protein levels, associated with enhanced glial production of IL-1β, TNFα, and IL-6 following LPS treatment.

    “Moreover, IL-4 knockout mice had reduced baseline expression of CD200 at mRNA and protein levels, which was associated with enhanced glial production of IL-1β, TNFα, and IL-6 following LPS treatment (Lyons et al, 2009).”

    From Microglia Priming with Aging and Stress (2017) · cites this paper as Lyons et al, 2009

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Authors
Lyons, A., McQuillan, K., Deighan, B. F., O’Reilly, J.-A., Downer, E. J., Murphy, A. C., Watson, M., Piazza, A., O’Connell, F., Griffin, R., Mills, K. H. G., & Lynch, M. A.
Affiliations
Trinity College Dublin (IE)
ORCID
Venue
Brain, Behavior, and Immunity
Publisher
Elsevier BV
Published
2009-10
Volume
23
Issue
7
Pages
1020-1027
ISSN
0889-1591 (ISSN-L)
DOI
10.1016/j.bbi.2009.05.060
OpenAlex
W2071341494
Cited by
98
References
41
Citations by year
2026: 2 · 2025: 4 · 2024: 6 · 2023: 1 · 2022: 2 · 2021: 5 · 2020: 9 · 2019: 9 · 2018: 9 · 2017: 4 · 2016: 8 · 2015: 3 · 2014: 4 · 2013: 10 · 2012: 7
FWCI
4.67
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • Brain Behavior and Immunity (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Science Foundation Ireland
  • Health Research Board
  • European Commission
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
Keywords
IL-4, CD200, CD200R, neuroinflammation, lipopolysaccharide, microglial activation, anti-inflammatory cytokines, IL-1β, exploratory behavior, neuromodulation, IL-4-deficient mice
MeSH terms
Analysis of Variance, Animals, Cells, Cultured, Cerebral Cortex, Enzyme-Linked Immunosorbent Assay, Exploratory Behavior, Fluorescent Antibody Technique, Hippocampus, Inflammation, Injections, Intraperitoneal, Lipopolysaccharides, Mice, Inbred C57BL, Neuroglia, Neurons, Antigens, CD, Interleukin-4, Cytokines, Mice, Knockout, Coculture Techniques, Reverse Transcriptase Polymerase Chain Reaction, Mice, Rats, Illness Behavior

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