ArticleNature neuroscience2011
MHCI negatively regulates synapse density during the establishment of cortical connections.
Article in Nature neuroscience, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 113 papers, 1 of them a synthesis that pooled it.
What it found
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Who cites it
113 citing papers in PubMed, 1 synthesis or guideline pooled it, 205 citations in OpenAlex.
- Linking Inflammation, Aberrant Glutamate-Dopamine Interaction, and Post-synaptic Changes: Translational Relevance for Schizophrenia and Antipsychotic Treatment: a Systematic Review.Molecular neurobiology · 2022Pooled it
- The neuroimmune system and cognition.Nature immunology · 2026Review
- Microglial replacement in a Sandhoff disease mouse model reveals myeloid-derived β-hexosaminidase is necessary for neuronal health.Nature communications · 2025Article
- Neurological Complications in Inborn Errors of Immunity: A Scoping Review of Clinical Spectrum, Pathophysiological Mechanisms, and Therapeutic Strategies.Clinical reviews in allergy & immunology · 2025Article
- Article
- Glutamate Signaling and Neuroligin/Neurexin Adhesion Play Opposing Roles That Are Mediated by Major Histocompatibility Complex I Molecules in Cortical Synapse Formation.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- CD8Brain, behavior, and immunity · 2024Article
- Myeloid-derived β-hexosaminidase is essential for neuronal health and lysosome function: implications for Sandhoff disease.bioRxiv : the preprint server for biology · 2024Article
- HLA-A, -B, -C and -DRB1 Association with Autism Spectrum Disorder Risk: A Sex-Related Analysis in Italian ASD Children and Their Siblings.International journal of molecular sciences · 2024Article
- Serum beta2-microglobulin acts as a biomarker for severity and prognosis in glioma patients: a preliminary clinical study.BMC cancer · 2024Article
- An innate immune response to adeno-associated virus genomes decreases cortical dendritic complexity and disrupts synaptic transmission.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- The Role of Beta2-Microglobulin in Central Nervous System Disease.Cellular and molecular neurobiology · 2024Review
- Maternal immunoglobulin G affects brain development of mouse offspring.Journal of neuroinflammation · 2024Article
- Article
- Microglia Modulate Neurodevelopment in Autism Spectrum Disorder and Schizophrenia.International journal of molecular sciences · 2023Review
- CD8+ T cells recognizing a neuron-restricted antigen injure axons in a model of multiple sclerosis.The Journal of clinical investigation · 2023Article
- Microglial MHC-I induction with aging and Alzheimer's is conserved in mouse models and humans.GeroScience · 2023Article
- Neuronal MHC-I complex is destabilized by amyloid-β and its implications in Alzheimer's disease.Cell & bioscience · 2023Article
- Brain-specific Pd1 deficiency leads to cortical neurogenesis defects and depressive-like behaviors in mice.Cell death and differentiation · 2023Article
- Outside-in signaling through the major histocompatibility complex class-I cytoplasmic tail modulates glutamate receptor expression in neurons.Scientific reports · 2023Article
53 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Major histocompatibility complex class I (MHCI) molecules modulate activity-dependent refinement and plasticity. We found that MHCI also negatively regulates the density and function of cortical synapses during their initial establishment both in vitro and in vivo. MHCI molecules are expressed on cortical neurons before and during synaptogenesis. In vitro, decreasing surface MHCI (sMHCI) on neurons increased glutamatergic and GABAergic synapse density, whereas overexpression decreased it. In vivo, synapse density was higher throughout development in β2m(-/-) mice. MHCI also negatively regulated the strength of excitatory, but not inhibitory, synapses and controlled the balance of excitation and inhibition onto cortical neurons. sMHCI levels were modulated by activity and were necessary for activity to negatively regulate glutamatergic synapse density. Finally, acute changes in sMHCI and activity altered synapse density exclusively during early postnatal development. These results identify a previously unknown function for immune proteins in the negative regulation of the initial establishment and function of cortical connections.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.