Control of glial immune function by neurons

Neumann, Harald

doi:10.1002/glia.1108

Cited by 319Neuroinflammation and Neurodegeneration MechanismsMultiple Sclerosis Research StudiesTryptophan and brain disorders

Control of glial immune function by neurons

Neumann, Harald·2001·Glia

DOI 10.1002/glia.1108

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Abstract

The immune status of the central nervous system (CNS) is strictly regulated. In the healthy brain, immune responses are kept to a minimum. In contrast, in a variety of inflammatory and neurodegenerative diseases, including multiple sclerosis, infections, trauma, stroke, neoplasia, and Alzheimer's disease, glial cells such as microglia gain antigen‐presenting capacity through the expression of major histocompatibility complex (MHC) molecules. Further, proinflammatory cytokines, such as tumor necrosis factor‐α (TNF), interleukin‐1β (IL‐1β), and interferon‐γ (IFN‐γ), as well as chemokines, are synthesized by resident brain cells and T lymphocytes invade the affected brain tissue. The proinflammatory cytokines stimulate microglial MHC expression in the lesioned CNS areas only. However, the induction of brain immunity is strongly counterregulated in intact CNS areas. For instance, recent work demonstrated that microglia are kept in a quiescent state in the intact CNS by local interactions between the microglia receptor CD200 and its ligand, which is expressed on neurons. Work done in our laboratory showed that neurons suppressed MHC expression in surrounding glial cells, in particular microglia and astrocytes. This control of MHC expression by neurons was dependent on their electrical activity. In brain tissue with intact neurons, the MHC class II inducibility of microglia and astrocytes by the proinflammatory cytokine IFN‐γ was reduced. Paralysis of neuronal electric activity by neurotoxins restored the induction of MHC molecules on microglia and astrocytes. Loss of neurons or their physiological activity would render the impaired CNS areas recognizable by invading T lymphocytes. Thus, immunity in the CNS is inhibited by the local microenvironment, in particular by physiologically active neurons, to prevent unwanted immune mediated damage of neurons. GLIA 36:191–199, 2001. © 2001 Wiley‐Liss, Inc.

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From Brain-Derived Neurotrophic Factor in Brain Disorders: Focus on Neuroinflammation (2019) · cites this paper as [38]

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Authors: Neumann, H.
Affiliations: European Neuroscience Institute Göttingen (DE)
Corresponding author: Neumann, Harald
ORCID: Neumann, Harald
Venue: Glia
Publisher: Wiley
Published: 2001-10-02
Volume: 36
Issue: 2
Pages: 191-199
ISSN: 0894-1491 (ISSN-L)
1098-1136
DOI: 10.1002/glia.1108
OpenAlex: W2041112741
Cited by: 319
References: 87
Citations by year: 2026: 1 · 2025: 3 · 2024: 7 · 2023: 5 · 2022: 2 · 2021: 6 · 2020: 8 · 2019: 5 · 2018: 12 · 2017: 6 · 2016: 12 · 2015: 13 · 2014: 21 · 2013: 25 · 2012: 13
FWCI: 2.01
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Glia (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
Keywords: neuron-glia interactions, microglia, astrocytes, MHC class II expression, CD200, neuronal electrical activity, interferon-gamma, inflammatory cytokines, neuroinflammation, neurodegenerative diseases, multiple sclerosis, Alzheimer's disease
MeSH terms: Animals, Cell Communication, Central Nervous System, Central Nervous System Diseases, Histocompatibility Antigens, Humans, Immunologic Surveillance, Neuroglia, Neurons, Microglia, Antigen Presentation

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