The DOI matches its Crossref record; 74 of the 74 references it cites were found in a registry or an index.
CNS: Not an immunoprivilaged site anymore but a virtual secondary lymphoid organ
Abstract
The cardinal dogma of central nervous system (CNS) immunology believed brain is an immune privileged site, but scientific evidences gathered so far have overturned this notion proving that CNS is no longer an immune privileged site, but rather an actively regulated site of immune surveillance. Landmark discovery of lymphatic system surrounding the duramater of the brain, made possible by high resolution live imaging technology has given new dimension to neuro-immunology. Here, we discuss the immune privilege status of CNS in light of the previous and current findings, taking into account the differences between a healthy state and changes that occur during an inflammatory response. Cerebrospinal fluid (CSF) along with interstitial fluid (ISF) drain activated T cells, natural killer cells, macrophages and dendritic cells from brain to regional lymph nodes present in the head and neck region. To keep an eye on inflammation, this system hosts an army of regulatory T cells (CD25+ FoxP3+) that regulate T cell hyper activation, proliferation and cytokine production. This review is an attempt to fill the gaps in our understanding of neuroimmune interactions, role of innate and adaptive immune system in maintaining homeostasis, interplay of different immune cells, immune tolerance, knowledge of communication pathways between the CNS and the peripheral immune system and lastly how interruption of immune surveillance leads to neurodegenerative diseases. We envisage that discoveries should be made not only to decipher underlying cellular and molecular mechanisms of immune trafficking, but should aid in identifying targeted cell populations for therapeutic intervention in neurodegenerative and autoimmune disorders.
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“However, the idea that the CNS is an immune privileged organ has been reconsidered, as the functional immune cells can enter the CNS through the BBB, the choroid plexus, and the lymphatic vessels and have been described beyond neuropathological conditions (26, 35–47).”
From The gut-brain axis: how microbiota and host inflammasome influence brain physiology and pathology (2020) · cites this paper as [40]
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“Among the molecules that can pass the BBB are also bacterial products and metabolites shaping not only the CNS development and functions (6, 15) but also the genesis of certain diseases (33–42).”
From The gut-brain axis: how microbiota and host inflammasome influence brain physiology and pathology (2020) · cites this paper as [40]
Citations
Cites
Park, J., Adoro, S., Guinter, T. I., Erman, B., Alag, A., Catálfamo, M., Kimura, M. Y., Cui, Y., Lucas, P. J., Gress, R. E., et al. (2010) · Nature Immunology · doi:10.1038/ni.1840 · Cited by 5,835
Sakaguchi, S., Sakaguchi, N., Asano, M., Itoh, M., & Toda, M. (1995) · The Journal of Immunology · doi:10.4049/jimmunol.155.3.1151 · Cited by 5,608 · cited 1×
“This subset of T cells, which develops with high avidity to self-antigens, is especially important in controlling autoimmunity [50].”
BackgroundFate Mapping Analysis Reveals That Adult Microglia Derive from Primitive Macrophages
Ginhoux, F., Greter, M., Leboeuf, M., Nandi, S., See, P., Gokhan, S., Mehler, M. F., Conway, S. J., Ng, L. G., Stanley, E. R., et al. (2010) · Science · doi:10.1126/science.1194637 · Cited by 5,175
Structural and functional features of central nervous system lymphatic vessels
Louveau, A., Smirnov, I., Keyes, T. J., Eccles, J. D., Rouhani, S. J., Peske, J. D., Derecki, N. C., Castle, D., Mandell, J. W., Lee, K. S., et al. (2015) · Nature · doi:10.1038/nature14432 · Cited by 4,413
A dural lymphatic vascular system that drains brain interstitial fluid and macromolecules
Aspelund, A., Antila, S., Proulx, S. T., Karlsen, T. V., Karaman, S., Detmar, M., Wiig, H., & Alitalo, K. (2015) · Journal of Experimental Medicine · doi:10.1084/jem.20142290 · Cited by 2,198
Immunology of multiple sclerosis
Sospedra, M., & Martin, R. (2005) · Annual Review of Immunology · doi:10.1146/annurev.immunol.23.021704.115707 · Cited by 2,149
Control of microglial neurotoxicity by the fractalkine receptor
Cardona, A. E., Pioro, E. P., Sasse, M. E., Kostenko, V., Cardona, S. M., Dijkstra, I. M., Huang, D., Kidd, G., Dombrowski, S., Dutta, R., et al. (2006) · Nature Neuroscience · doi:10.1038/nn1715 · Cited by 1,531
T‐lymphocyte entry into the central nervous system
Hickey, W. F., Hsu, B. L., & Kimura, H. (1991) · Journal of Neuroscience Research · doi:10.1002/jnr.490280213 · Cited by 1,176
Medawar, P. B. (1948) · PubMed · Cited by 1,084
Innate immunity in the central nervous system
Ransohoff, R. M., & Brown, M. A. (2012) · Journal of Clinical Investigation · doi:10.1172/jci58644 · Cited by 1,034
Research works printed but not linked: 13
- Medawar PB, Br J Exp Pathol, 29, 58
- Wekerle H, J Infect Dis, 186, s140
- Ehrlich P, Das sauerstufbudurfnis des organismus. Eine Farbenanalytische Studie
- Goldmann EE, Abhandl Konigl preuss Akad Wiss., 1, 1
- Weller RO, Pathophysiol Off J Int Soc Pathophysiol/ISP, 17, 295
- Kaplan HJ, Chem Immunol Allergy, 92, 11
- Szczepanik M., J Physiol Pharmacol, 62, 159
- F1 S, Immunol Rev, 248, 216
- Wekerle H, JID, 186, S140
- Ginhoux F, Front Cell Neurosci, 17, 45
- Tian L, J Neuroinflammation, 2, 155
- Shrestha R, J Neurosci Res, 28, 254
- London A, Front Cell Neurosci, 7, 34
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Lin, Z., Zhou, D., Jiang, J., Kwan, P., & Tian, X. Y. (2026) · Genes & Diseases · doi:10.1016/j.gendis.2026.102240
Jiang, Y., Xu, C., Jin, J., Liu, X. Z., Cai, H., Zhang, W., Zheng, X., Wu, J. I. A. H. U. I., Wang, Z., Piao, Y. S., et al. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1818028
Song, B., Wang, W., Liu, S., Jin, X., Yan, Q., Li, M., Yue, D., Liu, Y., Li, X., Yin, L., et al. (2026) · Aging Cell · doi:10.1111/acel.70699
Metadata
- Authors
- Negi, N., & Das, B. K.
- Affiliations
- Umeå University (SE)
- All India Institute of Medical Sciences (IN)
- Corresponding author
- Das, Bimal K.
- Venue
- International Reviews of Immunology
- Publisher
- Informa UK Limited
- Published
- 2017-09-29
- Volume
- 37
- Issue
- 1
- Pages
- 57-68
- ISSN
- 0883-0185 (ISSN-L)
- 1563-5244
- OpenAlex
- W2760038100
- Cited by
- 123
- References
- 74
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 11 · 2023: 19 · 2022: 14 · 2021: 27 · 2020: 17 · 2019: 7 · 2018: 13 · 2017: 1
- FWCI
- 1.00
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- International Reviews of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Clinical Neurology › Cerebrospinal fluid and hydrocephalus
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Keywords
- immune privilege, cerebrospinal fluid, interstitial fluid, immune surveillance, regulatory T cells, neuroinflammation, neuroimmune interactions, immune tolerance, neurodegenerative diseases, autoimmune disease, dendritic cells, macrophages, natural killer cells
- MeSH terms
- Alzheimer Disease, Animals, Central Nervous System, Encephalomyelitis, Autoimmune, Experimental, Humans, Immunologic Surveillance, Lymphatic System, Macrophages, Models, Neurological, Monocytes, Multiple Sclerosis, Parkinson Disease, Neuroimmunomodulation, Microglia, Antigen Presentation, Models, Immunological, Mice
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