Revisiting the Mechanisms of CNS Immune Privilege

Louveau, Antoine; Harris, Tajie H.; Kipnis, Jonathan

doi:10.1016/j.it.2015.08.006

Cited by 686Neuroinflammation and Neurodegeneration MechanismsBarrier Structure and Function StudiesCerebrospinal fluid and hydrocephalus

Revisiting the Mechanisms of CNS Immune Privilege

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Louveau, Antoine, Harris, Tajie H., Kipnis, Jonathan·2015·Trends in Immunology

DOI 10.1016/j.it.2015.08.006PMC PMC4593064

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Abstract

Whereas the study of the interactions between the immune system and the central nervous system (CNS) has often focused on pathological conditions, the importance of neuroimmune communication in CNS homeostasis and function has become clear over that last two decades. Here we discuss the progression of our understanding of the interaction between the peripheral immune system and the CNS. We examine the notion of immune privilege of the CNS in light of both earlier findings and recent studies revealing a functional meningeal lymphatic system that drains cerebrospinal fluid (CSF) to the deep cervical lymph nodes, and consider the implications of a revised perspective on the immune privilege of the CNS on the etiology and pathology of different neurological disorders.

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The CNS is considered an immune privileged site where inflammation and fibrosis are more subdued than elsewhere in the body.
“Additionally, while the CNS is considered an immune privileged site (Louveau et al., 2015) where inflammation and fibrosis are more subdued than elsewhere in the body, the peripheral nervous system develops the typical severity of FBR (Spearman et al., 2018).”
From Foreign Body Reaction to Implanted Biomaterials and Its Impact in Nerve Neuroprosthetics (2021) · cites this paper as Louveau et al., 2015

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A Unique Microglia Type Associated with Restricting Development of Alzheimer’s Disease
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The Microenvironmental Landscape of Brain Tumors
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Dendritic cell migration in health and disease
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The therapeutic potential of nanobodies
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Human and nonhuman primate meninges harbor lymphatic vessels that can be visualized noninvasively by MRI.
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Understanding the functions and relationships of the glymphatic system and meningeal lymphatics
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Single-cell analysis reveals T cell infiltration in old neurogenic niches
Dulken, B. W., Buckley, M. T., Navarro Negredo, P., Saligrama, N., Cayrol, R., Leeman, D. S., George, B. M., Boutet, S. C., Hebestreit, K., Pluvinage, J. V., et al. (2019) · Nature · doi:10.1038/s41586-019-1362-5 · Cited by 521 · see citing works
The Meningeal Lymphatic System: A New Player in Neurophysiology
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Foreign Body Reaction to Implanted Biomaterials and Its Impact in Nerve Neuroprosthetics
Carnicer-Lombarte, A., Chen, S.-T., Malliaras, G. G., & Barone, D. G. (2021) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2021.622524 · Cited by 454 · see citing works
“Additionally, while the CNS is considered an immune privileged site (Louveau et al., 2015) where inflammation and fibrosis are more subdued than elsewhere in the body, the peripheral nervous system develops the typical severity of FBR (Spearman et al.”
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Glymphatic System Impairment in Alzheimer’s Disease and Idiopathic Normal Pressure Hydrocephalus
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Molecular Heterogeneity and Immunosuppressive Microenvironment in Glioblastoma
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Myeloid Cells in the Central Nervous System
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Role of the JAK/STAT signaling pathway in regulation of innate immunity in neuroinflammatory diseases
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Delayed Cerebral Ischemia after Subarachnoid Hemorrhage: Beyond Vasospasm and Towards a Multifactorial Pathophysiology
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A journey into the brain: insight into how bacterial pathogens cross blood–brain barriers
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Anti-Inflammatory Effects of Resveratrol: Mechanistic Insights
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Contribution of neuroinflammation and immunity to brain aging and the mitigating effects of physical and cognitive interventions
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Neuroinflammation after surgery: from mechanisms to therapeutic targets
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Treatment of brain metastases with stereotactic radiosurgery and immune checkpoint inhibitors: An international meta-analysis of individual patient data
Lehrer, E. J., Peterson, J., Brown, P. D., Sheehan, J. P., Quiñones‐Hinojosa, A., Zaorsky, N. G., & Trifiletti, D. M. (2018) · Radiotherapy and Oncology · doi:10.1016/j.radonc.2018.08.025 · Cited by 267 · see citing works
Immune Evasion Strategies of Glioblastoma
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Unlocking the Power of Exosomes for Crossing Biological Barriers in Drug Delivery
Elliott, R. O., & He, M. (2021) · Pharmaceutics · doi:10.3390/pharmaceutics13010122 · Cited by 263 · see citing works
Lymphatic drainage system of the brain: A novel target for intervention of neurological diseases
Sun, B., Wang, L.-H., Yang, T., Sun, J., Mao, L., Yang, M., Yuan, H., Colvin, R. A., & Yang, X. (2017) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2017.08.007 · Cited by 255 · see citing works
Brain borders at the central stage of neuroimmunology
Rustenhoven, J., & Kipnis, J. (2022) · Nature · doi:10.1038/s41586-022-05474-7 · Cited by 253 · see citing works
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Aging and Rejuvenation of Neural Stem Cells and Their Niches
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Neurological Disease as a Failure of Brain-Immune Crosstalk: The Multiple Faces of Neuroinflammation
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Genetically engineered T cells for cancer immunotherapy
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Immunotherapy: a promising approach for glioma treatment
Yasinjan, F., Xing, Y., Geng, H., Guo, R., Yang, L., Liu, Z., & Wang, H. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1255611 · Cited by 238 · see citing works
Tissue reservoirs of HIV
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Protective Functions of Reactive Astrocytes Following Central Nervous System Insult
Linnerbauer, M., & Rothhammer, V. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.573256 · Cited by 221 · see citing works
Immune Cell Gene Signatures for Profiling the Microenvironment of Solid Tumors
Nirmal, A. J., Regan, T. W., Shih, B. B.-J., Hume, D. A., Sims, A. H., & Freeman, T. C. (2018) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-18-0342 · Cited by 219 · see citing works
Organ-specific protection mediated by cooperation between vascular and epithelial barriers
Spadoni, I., Fornasa, G., & Rescigno, M. (2017) · Nature reviews. Immunology · doi:10.1038/nri.2017.100 · Cited by 203 · see citing works
The Immune Privilege of the Intervertebral Disc: Implications for Intervertebral Disc Degeneration Treatment
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Immunotherapy for glioblastoma: the promise of combination strategies
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Neurodegenerative Disease and the NLRP3 Inflammasome
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Outside in: Unraveling the Role of Neuroinflammation in the Progression of Parkinson's Disease
Troncoso-Escudero, P., Parra, A., Nassif, M., & Vidal, R. L. (2018) · Frontiers in Neurology · doi:10.3389/fneur.2018.00860 · Cited by 191 · see citing works
Cerebral dysfunctions caused by sepsis during ageing
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Th17 cells in depression
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How Do Meningeal Lymphatic Vessels Drain the CNS?
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Lymphatics in Neurological Disorders: A Neuro-Lympho-Vascular Component of Multiple Sclerosis and Alzheimer’s Disease?
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Interleukin-2 improves amyloid pathology, synaptic failure and memory in Alzheimer’s disease mice
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Pain-resolving immune mechanisms in neuropathic pain
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The Role of Glucocorticoids in Inflammatory Diseases
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The Kynurenine Pathway is a Double-Edged Sword in Immune-Privileged Sites and in Cancer: Implications for Immunotherapy
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Heterogeneity in the lymphatic vascular system and its origin
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Insights on the pathophysiology of Alzheimer's disease: The crosstalk between amyloid pathology, neuroinflammation and the peripheral immune system
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Anti-Inflammatory Effects of GLP-1 Receptor Activation in the Brain in Neurodegenerative Diseases
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Suppressed immune microenvironment and repertoire in brain metastases from patients with resected non-small-cell lung cancer
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Tissue-specific Tregs in cancer metastasis: opportunities for precision immunotherapy
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Immune Checkpoint Inhibitors in Human Glioma Microenvironment
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“Inflamed” depression: A review of the interactions between depression and inflammation and current anti-inflammatory strategies for depression
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Mechanisms of NLRP3 priming in inflammaging and age related diseases
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Tumor hypoxia represses γδ T cell-mediated antitumor immunity against brain tumors
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Harnessing regulatory T cell neuroprotective activities for treatment of neurodegenerative disorders
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Multiple sclerosis: molecular pathogenesis and therapeutic intervention
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Extracellular vesicles are increased in the serum of children with autism spectrum disorder, contain mitochondrial DNA, and stimulate human microglia to secrete IL-1β
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The choroid plexus is a key cerebral invasion route for T cells after stroke
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Peripherally induced brain tissue–resident memory CD8+ T cells mediate protection against CNS infection
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CNS: Not an immunoprivilaged site anymore but a virtual secondary lymphoid organ
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Updates on immunity and inflammation in Parkinson disease pathology
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Current Understanding of Natural Antibodies and Exploring the Possibilities of Modulation Using Veterinary Models. A Review
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Authors: Louveau, A., Harris, T. H., & Kipnis, J.
Affiliations: University of Virginia (US)
Corresponding author: Kipnis, Jonathan
ORCID: Louveau, Antoine
Harris, Tajie H.
Kipnis, Jonathan
Venue: Trends in Immunology
Publisher: Elsevier BV
Published: 2015-10
Volume: 36
Issue: 10
Pages: 569-577
ISSN: 1471-4906 (ISSN-L)
DOI: 10.1016/j.it.2015.08.006
PMC: PMC4593064
OpenAlex: W1918237073
Cited by: 682
References: 105
Citations by year: 2026: 41 · 2025: 55 · 2024: 70 · 2023: 72 · 2022: 72 · 2021: 73 · 2020: 71 · 2019: 61 · 2018: 79 · 2017: 58 · 2016: 30
FWCI: 4.44
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Trends in Immunology (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health
National Institute on Aging (AG034113, R01AG034113, R37AG034113)
National Institute of Neurological Disorders and Stroke (R01NS091067)
Topics: Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Cerebrospinal fluid and hydrocephalus
Keywords: neuroimmune interactions, meningeal lymphatic system, cerebrospinal fluid drainage, deep cervical lymph nodes, peripheral immune system, CNS homeostasis, neurological disorders, neuroinflammation
MeSH terms: Animals, Central Nervous System, Central Nervous System Diseases, Humans, Immune System, Lymphatic Diseases, Lymphatic System

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Revisiting the Mechanisms of CNS Immune Privilege

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