Immune proteins in brain development and synaptic plasticity
Open accessAbstract
Many proteins first identified in the immune system are also expressed in the developing and adult nervous system. Unexpectedly, recent studies reveal that a number of these proteins, in addition to their immunological roles, are essential for the establishment, function, and modification of synaptic connections. These include proinflammatory cytokines (e.g., TNFalpha, IL-6), proteins of the innate immune system (e.g., complement C1q and C3, pentraxins, Dscam), members of the major histocompatibility complex class I (MHCI) family, and MHCI-binding immunoreceptors and their components (e.g., PIRB, Ly49, DAP12, CD3zeta). Understanding how these proteins function in neurons will clarify the molecular basis of fundamental events in brain development and plasticity and may add a new dimension to our understanding of neural-immune interactions in health and disease.
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During normal brain development, microglia engulf synapses and sculpt synaptic connections via a role for complement.
“During normal brain development, mounting evidence indicates that microglia engulf synapses and sculpt synaptic connections via a novel role for complement, a component of the innate immune system that enhances the clearance of microbes or damaged cells by phagocytes (Boulanger, 2009; Stephan et al., 2012; Chung et al., 2015).”
From Microglia in Alzheimer’s disease (2018) · cites this paper as Boulanger, 2009
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Interleukin-1β increases synaptic inhibition in rat hippocampal pyramidal neurons in vitro
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CD3 and Immunoglobulin G Fc Receptor Regulate Cerebellar Functions
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Cutting Edge: MHC Class I–Ly49 Interaction Regulates Neuronal Function
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Narp and NP1 Form Heterocomplexes that Function in Developmental and Activity-Dependent
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Microglia in Alzheimer’s disease
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“…copy number and expression of complement factor C4A (Sekar et al., 2016), and genetic variants in complement proteins and regulators (most notably CFH) that lead to increased complement activity are highly associated with age-related macular degeneration (Klein et al., 2005; Boyer et al., 2017).”
BackgroundTranscriptomic Analysis of Autistic Brain Reveals Convergent Molecular Pathology
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The Sleep-Immune Crosstalk in Health and Disease
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“Alternative routes of immune-to-brain signaling are immunomediators that can activate vagal and other neural afferents, as well as cerebral endothelial and perivascular cells or the directed traffic of leukocytes to the brain (70, 503, 523, 586).”
BackgroundThe Complement System: An Unexpected Role in Synaptic Pruning During Development and Disease
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The environment and susceptibility to schizophrenia
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The “quad‐partite” synapse: Microglia‐synapse interactions in the developing and mature CNS
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The Role of the Immune System in Autism Spectrum Disorder
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Bialas, A. R., & Stevens, B. (2013) · Nature Neuroscience · doi:10.1038/nn.3560 · Cited by 519 · see citing works
RetractedA Dramatic Increase of C1q Protein in the CNS during Normal Aging
Stephan, A. H., Madison, D. V., Mateos, J. M., Fraser, D. A., Lovelett, E. A., Coutellier, L., Kim, L., Tsai, H.-H., Huang, E. J., Rowitch, D. H., et al. (2013) · The Journal of Neuroscience · doi:10.1523/jneurosci.1333-13.2013 · Cited by 423 · see citing works
Psychoneuroimmunology of early-life stress: the hidden wounds of childhood trauma?
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Role of microglia in CNS inflammation
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“development and plasticity, potentially disrupting the establishment and modification of brain circuitry [58].”
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An age-related sprouting transcriptome provides molecular control of axonal sprouting after stroke
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Hidden wounds? inflammatory links between childhood trauma and psychopathology
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The dual roles of cytokines in Alzheimer’s disease: update on interleukins, TNF-α, TGF-β and IFN-γ
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Sex, glia, and development: Interactions in health and disease
Schwarz, J. M., & Bilbo, S. D. (2012) · Hormones and Behavior · doi:10.1016/j.yhbeh.2012.02.018 · Cited by 247 · see citing works
Garay, P. (2010) · Frontiers in Synaptic Neuroscience · doi:10.3389/fnsyn.2010.00136 · Cited by 217 · see citing works
Semaphorins guide the entry of dendritic cells into the lymphatics by activating myosin II
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Major histocompatibility complex class I proteins in brain development and plasticity
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Phagocytic glial cells: sculpting synaptic circuits in the developing nervous system
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Calcium signaling and gliotransmission in normal vs. reactive astrocytes
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Fever and sickness behavior: Friend or foe?
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Neuroimmune regulation of homeostatic synaptic plasticity
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Gene expression studies in autism: Moving from the genome to the transcriptome and beyond
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Neuropoietic cytokines in normal brain development and neurodevelopmental disorders
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Neuroendocrine-Immune Crosstalk Shapes Sex-Specific Brain Development
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- Authors
- Boulanger, L. M.
- Affiliations
- Princeton University (US)
- Corresponding author
- Boulanger, Lisa M.
- ORCID
- Boulanger, Lisa M.
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2009-10
- Volume
- 64
- Issue
- 1
- Pages
- 93-109
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2091389527
- Cited by
- 555
- References
- 116
- Citations by year
- 2026: 20 · 2025: 18 · 2024: 36 · 2023: 34 · 2022: 21 · 2021: 33 · 2020: 28 · 2019: 31 · 2018: 40 · 2017: 36 · 2016: 34 · 2015: 31 · 2014: 35 · 2013: 43 · 2012: 42
- FWCI
- 3.01
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- immune proteins, brain development, synaptic plasticity, inflammatory cytokines, TNF-α, interleukin-6, C1q, complement C3, pentraxins, Dscam, MHC class I, immunoreceptors, PirB, Ly49, DAP12, CD3zeta, neuroimmune interactions
- MeSH terms
- Animals, Brain, Humans, Neuronal Plasticity, Neurons, Synapses, Neuroimmunomodulation, Signal Transduction
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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