CNS: Not an immunoprivilaged site anymore but a virtual secondary lymphoid organ

Negi, Neema; Das, Bimal K.

doi:10.1080/08830185.2017.1357719

Cited by 123Neuroinflammation and Neurodegeneration MechanismsCerebrospinal fluid and hydrocephalusBarrier Structure and Function Studies

CNS: Not an immunoprivilaged site anymore but a virtual secondary lymphoid organ

Negi, Neema, Das, Bimal K.·2018·International Reviews of Immunology

DOI 10.1080/08830185.2017.1357719

Open this paper in CoChat — free account

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.

Integrity signals

Registry

Crossref · 10.1080/08830185.2017.1357719

Cites

74 of 74 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Functional immune cells can enter the CNS through the blood-brain barrier, choroid plexus, and lymphatic vessels and have been described beyond neuropathological conditions.
“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]
Bacterial products and metabolites can pass the blood-brain barrier and shape CNS development and functions and the genesis of certain diseases.
“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]

Signaling by intrathymic cytokines, not T cell antigen receptors, specifies CD8 lineage choice and promotes the differentiation of cytotoxic-lineage T cells
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 · see citing works
Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor α-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases
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 · see citing works
Fate 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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
Immunity to homologous grafted skin; the fate of skin homografts transplanted to the brain, to subcutaneous tissue, and to the anterior chamber of the eye.
Medawar, P. B. (1948) · PubMed · Cited by 1,084 · see citing works
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 · see citing works
The anatomical and cellular basis of immune surveillance in the central nervous system
Ransohoff, R. M., & Engelhardt, B. (2012) · Nature reviews. Immunology · doi:10.1038/nri3265 · Cited by 975 · see citing works
Origin and differentiation of microglia
Ginhoux, F., Lim, S., Hoeffel, G., Low, D., & Huber, T. (2013) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2013.00045 · Cited by 905 · cited 1× · see citing works
“are highly specialized tissue macrophages present in healthy CNS [28].”
Background
CNS immune privilege: hiding in plain sight
Carson, M. J., Doose, J. M., Melchior, B., Schmid, C. D., & Ploix, C. C. (2006) · Immunological Reviews · doi:10.1111/j.1600-065x.2006.00441.x · Cited by 801 · see citing works
The origin and nature of ramified and amoeboid microglia: A historical review and current concepts
Ling, E., & Wong, W.-C. (1993) · Glia · doi:10.1002/glia.440070105 · Cited by 690 · see citing works
Revisiting the Mechanisms of CNS Immune Privilege
Louveau, A., Harris, T. H., & Kipnis, J. (2015) · Trends in Immunology · doi:10.1016/j.it.2015.08.006 · Cited by 682 · see citing works
TGF-β1 promotes microglial amyloid-β clearance and reduces plaque burden in transgenic mice
Wyss-Coray, T., Lin, C., Yan, F., Yu, G.-Q., Rohde, M., McConlogue, L., Masliah, E., & Mucke, L. (2001) · Nature Medicine · doi:10.1038/87945 · Cited by 587 · see citing works
Trafficking of immune cells in the central nervous system
Wilson, E. H., Weninger, W., & Hunter, C. A. (2010) · Journal of Clinical Investigation · doi:10.1172/jci41911 · Cited by 521 · see citing works
Chemokine Expression by Glial Cells Directs Leukocytes to Sites of Axonal Injury in the CNS
Babcock, A. A., Kuziel, W. A., Rivest, S., & Owens, T. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-21-07922.2003 · Cited by 472 · see citing works
CNS myeloid DCs presenting endogenous myelin peptides 'preferentially' polarize CD4+ TH-17 cells in relapsing EAE
Bailey, S. L., Schreiner, B., McMahon, E., & Miller, S. D. (2007) · Nature Immunology · doi:10.1038/ni1430 · Cited by 463 · see citing works
Immune surveillance in multiple sclerosis patients treated with natalizumab
Stüve, O., Marra, C. M., Jerome, K. R., Cook, L., Cravens, P. D., Cepok, S., Frohman, E. M., Phillips, J. T., Arendt, G., Hemmer, B., et al. (2006) · Annals of Neurology · doi:10.1002/ana.20858 · Cited by 434 · see citing works
Blocking TGF-β–Smad2/3 innate immune signaling mitigates Alzheimer-like pathology
Town, T., Laouar, Y., Pittenger, C., Mori, T., Szekely, C. A., Tan, J., Duman, R. S., & Flavell, R. A. (2008) · Nature Medicine · doi:10.1038/nm1781 · Cited by 422 · see citing works
Amyloidogenic role of cytokine TGF-β1 in transgenic mice and in Alzheimer's disease
Wyss-Coray, T., Masliah, E., Mallory, M., McConlogue, L., Johnson-Wood, K., Lin, C., & Mucke, L. (1997) · Nature · doi:10.1038/39321 · Cited by 417 · see citing works
The role of microglia in central nervous system immunity and glioma immunology
Yang, I., Han, S. J., Kaur, G., Crane, C., & Parsa, A. T. (2010) · Journal of Clinical Neuroscience · doi:10.1016/j.jocn.2009.05.006 · Cited by 410 · cited 1× · see citing works
“1, CD40, CD80, and CD86 on their surface [36].”
Background
Decreased FOXP3 levels in multiple sclerosis patients
Huan, J., Culbertson, N. E., Spencer, L., Bartholomew, R. M., Burrows, G. G., Chou, Y. K., BOURDETTE, D. N., Ziegler, S. F., Offner, H., & Vandenbark, A. A. (2005) · Journal of Neuroscience Research · doi:10.1002/jnr.20522 · Cited by 369 · see citing works
Molecular mechanisms involved in T cell migration across the blood–brain barrier
Engelhardt, B. (2006) · Journal of Neural Transmission · doi:10.1007/s00702-005-0409-y · Cited by 344 · see citing works
Mini‐review: Transendothelial migration of leukocytes: through the front door or around the side of the house?
Engelhardt, B., & Wolburg, H. (2004) · European Journal of Immunology · doi:10.1002/eji.200425327 · Cited by 334 · see citing works
Microglia: gatekeepers of central nervous system immunology
Tambuyzer, B. R., Ponsaerts, P., & Nouwen, E. J. (2008) · Journal of Leukocyte Biology · doi:10.1189/jlb.0608385 · Cited by 331 · see citing works
Control of glial immune function by neurons
Neumann, H. (2001) · Glia · doi:10.1002/glia.1108 · Cited by 319 · see citing works
Regulatory CD4+ T Cells Expressing Endogenous T Cell Receptor Chains Protect Myelin Basic Protein–specific Transgenic Mice from Spontaneous Autoimmune Encephalomyelitis
Olivares–Villagómez, D., Wang, Y., & Lafaille, J. J. (1998) · The Journal of Experimental Medicine · doi:10.1084/jem.188.10.1883 · Cited by 294 · see citing works
Microglia and monocyte-derived macrophages: functionally distinct populations that act in concert in CNS plasticity and repair
London, A., Cohen, M., & Schwartz, M. (2013) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2013.00034 · Cited by 282 · see citing works
A revised view of the central nervous system microenvironment and major histocompatibility complex class II antigen presentation
Perry, V. H. (1998) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(98)00145-3 · Cited by 276 · see citing works
Altered CD4+/CD8+ T-Cell Ratios in Cerebrospinal Fluid of Natalizumab-Treated Patients With Multiple Sclerosis
Stüve, O., Marra, C. M., Bar‐Or, A., Niino, M., Cravens, P. D., Cepok, S., Frohman, E. M., Phillips, J. T., Arendt, G., Jerome, K. R., et al. (2006) · Archives of Neurology · doi:10.1001/archneur.63.10.1383 · Cited by 271 · see citing works
Fas ligand/Fas system in the brain: regulator of immune and apoptotic responses
Choi, C., & Benveniste, E. N. (2004) · Brain Research Reviews · doi:10.1016/j.brainresrev.2003.08.007 · Cited by 270 · see citing works
Mesenteric Vasodilation Mediated by Endothelial Anandamide Receptors
Wagner, J. A., Varga, K., Járai, Z., & Kunos, G. (1999) · Hypertension · doi:10.1161/01.hyp.33.1.429 · Cited by 257 · see citing works
Fluids and barriers of the CNS establish immune privilege by confining immune surveillance to a two-walled castle moat surrounding the CNS castle
Engelhardt, B., & Coisne, C. (2011) · Fluids and Barriers of the CNS · doi:10.1186/2045-8118-8-4 · Cited by 247 · see citing works
The role of regulatory T cells in multiple sclerosis
Zozulya, A. L., & Wiendl, H. (2008) · Nature Clinical Practice Neurology · doi:10.1038/ncpneuro0832 · Cited by 241 · see citing works
Neuroimmune crosstalk in the central nervous system and its significance for neurological diseases
Tian, L., Ma, L., Kaarela, T., & Li, Z. (2012) · Journal of Neuroinflammation · doi:10.1186/1742-2094-9-155 · Cited by 220 · see citing works
Flt3L controls the development of radiosensitive dendritic cells in the meninges and choroid plexus of the steady-state mouse brain
Anandasabapathy, N., Victora, G. D., Meredith, M. M., Feder, R. E., Dong, B., Kluger, C., Yao, K.-H., Dustin, M. L., Nussenzweig, M. C., Steinman, R. M., et al. (2011) · The Journal of Experimental Medicine · doi:10.1084/jem.20102657 · Cited by 207 · see citing works
Defects in CD8+ Regulatory T Cells in the Lamina Propria of Patients with Inflammatory Bowel Disease
Brimnes, J., Allez, M., Dotan, I., Shao, L., Nakazawa, A., & Mayer, L. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.174.9.5814 · Cited by 187 · see citing works
T‐cell trafficking in the central nervous system
Sallusto, F., Impellizzieri, D., Basso, C., Laroni, A., Uccelli, A., Lanzavecchia, A., & Engelhardt, B. (2012) · Immunological Reviews · doi:10.1111/j.1600-065x.2012.01140.x · Cited by 186 · see citing works
Secondary progressive in contrast to relapsing‐remitting multiple sclerosis patients show a normal CD4+CD25+ regulatory T‐cell function and FOXP3 expression
Venken, K., Hellings, N., Hensen, K., Rummens, J., Medaer, R., D'hooghe, M. B., Dubois, B., Raus, J., & Stinissen, P. (2006) · Journal of Neuroscience Research · doi:10.1002/jnr.20852 · Cited by 185 · see citing works
T-Cells in Alzheimer's Disease
Town, T., Tan, J., Flavell, R. A., & Mullan, M. (2005) · NeuroMolecular Medicine · doi:10.1385/nmm:7:3:255 · Cited by 183 · see citing works
Phenotypic and functional analysis of T cells homing into the CSF of subjects with inflammatory diseases of the CNS
Giunti, D., Borsellino, G., Benelli, R., Marchese, M., Capello, E., Valle, M. T., Pedemonte, E., Noonan, D. M., Albini, A., Bernardi, G., et al. (2003) · Journal of Leukocyte Biology · doi:10.1189/jlb.1202598 · Cited by 180 · see citing works
Brain dendritic cells: biology and pathology
D’Agostino, P. M., Gottfried‐Blackmore, A., Anandasabapathy, N., & Bulloch, K. (2012) · Acta Neuropathologica · doi:10.1007/s00401-012-1018-0 · Cited by 176 · see citing works
Selective ablation of bone marrow‐derived dendritic cells increases amyloid plaques in a mouse Alzheimer's disease model
Butovsky, O., Kunis, G., Koronyo‐Hamaoui, M., & Schwartz, M. (2007) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2007.05652.x · Cited by 167 · see citing works
Drainage of Cells and Soluble Antigen from the CNS to Regional Lymph Nodes
Laman, J. D., & Weller, R. O. (2013) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-013-9470-8 · Cited by 165 · see citing works
CD4+CD25+FoxP3+ T lymphocytes fail to suppress myelin basic protein-induced proliferation in patients with multiple sclerosis
Baranwal, M., Putzki, N., Limmroth, V., Remus, R., Lindemann, M., Knop, D., Mueller, N., Hardt, C., Kreuzfelder, E., & Grosse‐Wilde, H. (2006) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2006.08.003 · Cited by 153 · see citing works
Pathophysiology of the lymphatic drainage of the central nervous system: Implications for pathogenesis and therapy of multiple sclerosis
Weller, R. O., Galea, I., Carare, R. O., & Minagar, A. (2009) · Pathophysiology · doi:10.1016/j.pathophys.2009.10.007 · Cited by 139 · see citing works
Interferon beta-1a therapy enhances CD4+ regulatory T-cell function: An ex vivo and in vitro longitudinal study in relapsing−remitting multiple sclerosis
de Andrés, C., Aristimuño, C., Heras, V. D. L., Martínez-Ginés, M. L., Bartolomé, M., Arroyo, R., Navarro, J., Giménez-Roldán, S., Fernández‐Cruz, E., & Sánchez‐Ramón, S. (2006) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2006.09.012 · Cited by 131 · see citing works
Comprehensive Immunophenotyping of Cerebrospinal Fluid Cells in Patients with Neuroimmunological Diseases
Han, S., Lin, Y. C., Wu, T., Salgado, A. D., Mexhitaj, I., Wuest, S. C., Romm, E., Ohayon, J. M., Goldbach‐Mansky, R. T., Vanderver, A. L., et al. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1302884 · Cited by 125 · see citing works
Ontogeny and Functions of Central Nervous System Macrophages
Katsumoto, A., Lu, H., Miranda, A. S., & Ransohoff, R. M. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1400716 · Cited by 124 · see citing works
Regulatory T cells in the central nervous system
Lowther, D. E., & Hafler, D. A. (2012) · Immunological Reviews · doi:10.1111/j.1600-065x.2012.01130.x · Cited by 123 · see citing works
HLA-E–restricted regulatory CD8+ T cells are involved in development and control of human autoimmune type 1 diabetes
Jiang, H., Canfield, S. M., Gallagher, M. P., Jiang, Y., Jiang, Y., Zheng, Z., & Chess, L. (2010) · Journal of Clinical Investigation · doi:10.1172/jci43522 · Cited by 118 · see citing works
Inflammasome-Derived IL-1β Regulates the Production of GM-CSF by CD4+ T Cells and γδ T Cells
Lukens, J. R., Barr, M., Chaplin, D., Chi, H., & Kanneganti, T. (2012) · The Journal of Immunology · doi:10.4049/jimmunol.1103308 · Cited by 117 · see citing works
Phagocytosis of ?/A4 amyloid fibrils of the neuritic neocortical plaques
Wisniewski, H. M., Barcikowska, M., & Kida, E. (1991) · Acta Neuropathologica · doi:10.1007/bf00310142 · Cited by 109 · see citing works
Potential roles for CD8+ T cells in rheumatoid arthritis
Carvalheiro, H., da Silva, J. A. P., & Souto‐Carneiro, M. (2012) · Autoimmunity Reviews · doi:10.1016/j.autrev.2012.07.011 · Cited by 108 · see citing works
Immune and Nervous Systems: More Than Just a Superficial Similarity?
Kioussis, D., & Pachnis, V. (2009) · Immunity · doi:10.1016/j.immuni.2009.09.009 · Cited by 105 · see citing works
Regulation of Immunity by a Novel Population of Qa-1-Restricted CD8αα+TCRαβ+ T Cells
Tang, X., Maricic, I., Purohit, N., Bakamjian, B., Abegglen, L. M., Beeston, T., Jensen, P. E., & Kumar, V. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.11.7645 · Cited by 95 · see citing works
T cell migration into the central nervous system during health and disease: Different molecular keys allow access to different central nervous system compartments
Engelhardt, B. (2010) · Clinical and Experimental Neuroimmunology · doi:10.1111/j.1759-1961.2010.009.x · Cited by 77 · see citing works
Cutting Edge: CNS CD11c+ Cells from Mice with Encephalomyelitis Polarize Th17 cells and Support CD25+CD4+ T cell-Mediated Immunosuppression, Suggesting Dual Roles in the Disease Process
Deshpande, P., King, I. L., & Segal, B. M. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.11.6695 · Cited by 75 · see citing works
Macrophages Are Eliminated from the Injured Peripheral Nerve via Local Apoptosis and Circulation to Regional Lymph Nodes and the Spleen
Kuhlmann, T., Bitsch, A., Stadelmann, C., Siebert, H., & Brück, W. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-10-03401.2001 · Cited by 68 · see citing works
Induction of macrophage inflammatory protein MIP-1α mRNA on glial cells after focal cerebral ischemia in the rat
Takami, S., Nishikawa, H., Minami, M., Nishiyori, A., Sato, M., Akaike, A., & Satoh, M. (1997) · Neuroscience Letters · doi:10.1016/s0304-3940(97)00338-8 · Cited by 67 · see citing works
Immune regulation of multiple sclerosis by CD8+ T cells
Sinha, S., Itani, F. R., & Karandikar, N. J. (2014) · Immunologic Research · doi:10.1007/s12026-014-8529-9 · Cited by 63 · see citing works
Modeling multiple sclerosis in laboratory animals
Schreiner, B., Heppner, F. L., & Becher, B. (2009) · Seminars in Immunopathology · doi:10.1007/s00281-009-0181-4 · Cited by 61 · see citing works
TGF-β–Induced Myelin Peptide-Specific Regulatory T Cells Mediate Antigen-Specific Suppression of Induction of Experimental Autoimmune Encephalomyelitis
Zhang, H., Podojil, J. R., Chang, J., Luo, X., & Miller, S. D. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.0904044 · Cited by 52 · see citing works
Is extravasation a Fas-regulated process?
Walsh, K., & Sata, M. (1999) · Molecular Medicine Today · doi:10.1016/s1357-4310(98)01415-4 · Cited by 48 · see citing works
Regulatory T Cells Selectively Preserve Immune Privilege of Self-Antigens during Viral Central Nervous System Infection
Cervantes‐Barragán, L., Firner, S., Bechmann, I., Waisman, A., Lahl, K., Sparwasser, T. D., Thiel, V., & Ludewig, B. (2012) · The Journal of Immunology · doi:10.4049/jimmunol.1102422 · Cited by 45 · see citing works
Stem cell therapy for central nerve system injuries: glial cells hold the key
Xiao, L., Saiki, C., & Ide, R. (2014) · Neural Regeneration Research · doi:10.4103/1673-5374.137570 · Cited by 44 · see citing works
GM‐CSF and M‐CSF modulate β‐chemokine and HIV‐1 expression in microglia
Si, Q., Cosenza, M., Zhao, M., Goldstein, H., & Lee, S. C. (2002) · Glia · doi:10.1002/glia.10095 · Cited by 35 · see citing works
Regional Immunity and Immune Privilege
Kaplan, H. J., & Niederkorn, J. Y. (2007) · KARGER eBooks · doi:10.1159/000099237 · Cited by 32 · see citing works
Is Central Nervous System an Immune-Privileged Site?
Shrestha, R., Millington, O. R., Brewer, J. M., & Bushell, T. J. (2014) · Kathmandu University Medical Journal · doi:10.3126/kumj.v11i1.11055 · Cited by 26 · see citing works
Mechanisms of immunological tolerance to the antigens of the central nervous system. Skin-induced tolerance as a new therapeutic concept.
Szczepanik, M. (2011) · PubMed · Cited by 10 · see citing works
Editorial: Route by which monocytes leave the brain is revealed
Laman, J. D., & Weller, R. O. (2012) · Journal of Leukocyte Biology · doi:10.1189/jlb.0212110 · Cited by 10 · see citing works
Increased activity of surviving locus ceruleus neurons in Alzheimer's disease
Moser (1999) · Pure Amsterdam UMC · doi:10.1002/1531-8249(199901)45:1

Flagged first, then by citations

Sorted by citations

The gut-brain axis: how microbiota and host inflammasome influence brain physiology and pathology
Rutsch, A., Kantsjö, J. B., & Ronchi, F. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.604179 · Cited by 821 · see citing works
Molecular mimicry and autoimmunity
Rojas, M., Restrepo-Jiménez, P., Monsalve, D. M., Pacheco, Y., Acosta-Ampudia, Y., Ramírez-Santana, C., Leung, P. S. C., Ansari, A. A., Gershwin, M. E., & Anaya, J.-M. (2018) · Journal of Autoimmunity · doi:10.1016/j.jaut.2018.10.012 · Cited by 627 · see citing works
Inflammatory Role of TLR-MyD88 Signaling in Multiple Sclerosis
Zheng, C., Chen, J., Chu, F., Zhu, J., & Jin, T. (2020) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2019.00314 · Cited by 150 · see citing works
Tissue-specific Tregs in cancer metastasis: opportunities for precision immunotherapy
Huppert, L., Green, M. D., Kim, L., Chow, C., Leyfman, Y., Daud, A., & Lee, J. C. (2021) · Cellular & Molecular Immunology · doi:10.1038/s41423-021-00742-4 · Cited by 123 · see citing works
Molecular Mechanisms of Drug Resistance in Glioblastoma
Dymova, M. A., Kuligina, E. V., & Richter, V. A. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22126385 · Cited by 136 · see citing works
Lung-brain axis
Bajinka, O., Simbilyabo, L., Tan, Y., Jabang, J. N., & Saleem, S. A. (2021) · Critical Reviews in Microbiology · doi:10.1080/1040841x.2021.1960483 · Cited by 128 · see citing works
Toll-like receptor-mediated neuroinflammation: relevance for cognitive dysfunctions
Squillace, S., & Salvemini, D. (2022) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2022.05.004 · Cited by 117 · see citing works
Glioblastoma Organoids: Pre-Clinical Applications and Challenges in the Context of Immunotherapy
Klein, E., Hau, A., Oudin, A., Golebiewska, A., & Niclou, S. P. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.604121 · Cited by 98 · see citing works
Convergent inducers and effectors of T cell paralysis in the tumour microenvironment
Hanahan, D., Michielin, O. A., & Pittet, M. J. (2024) · Nature reviews. Cancer · doi:10.1038/s41568-024-00761-z · Cited by 102 · see citing works
Brain Injury–Mediated Neuroinflammatory Response and Alzheimer’s Disease
Kempuraj, D., Ahmed, M. E., Selvakumar, G. P., Thangavel, R., Dhaliwal, A. S., Dubova, I., Mentor, S., Premkumar, K., Saeed, D., Zahoor, H., et al. (2019) · The Neuroscientist · doi:10.1177/1073858419848293 · Cited by 87 · see citing works
Targeting brain-peripheral immune responses for secondary brain injury after ischemic and hemorrhagic stroke
Duan, M., Xu, Y., Li, Y., Feng, H., & Chen, Y. (2024) · Journal of Neuroinflammation · doi:10.1186/s12974-024-03101-y · Cited by 82 · see citing works
Cross-Talk of the CNS With Immune Cells and Functions in Health and Disease
Matejuk, A., Vandenbark, A. A., & Offner, H. (2021) · Frontiers in Neurology · doi:10.3389/fneur.2021.672455 · Cited by 79 · see citing works
Common Peripheral Immunity Mechanisms in Multiple Sclerosis and Alzheimer's Disease
Rossi, B., Santos-Lima, B., Terrabuio, E., Zenaro, E., & Constantin, G. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.639369 · Cited by 79 · see citing works
The Role of Microglia in Perioperative Neuroinflammation and Neurocognitive Disorders
Saxena, S., Kruys, V., Vamecq, J., & Maze, M. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.671499 · Cited by 73 · see citing works
Role of Peripheral Immune Cells-Mediated Inflammation on the Process of Neurodegenerative Diseases
Yang, Q., Wang, G., & Zhang, F. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.582825 · Cited by 71 · see citing works
Toll-like receptors and NLRP3 inflammasome-dependent pathways in Parkinson’s disease: mechanisms and therapeutic implications
Soraci, L., Gambuzza, M. E., Biscetti, L., Laganà, P., Russo, C. L., Buda, A., Barresi, G., Corsonello, A., Lattanzio, F., Lorello, G., et al. (2022) · Journal of Neurology · doi:10.1007/s00415-022-11491-3 · Cited by 71 · see citing works
Blood‒Brain Barrier Pathology and CNS Outcomes in Streptococcus pneumoniae Meningitis
Yau, B., Hunt, N. H., Mitchell, A. J., & Too, L. K. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19113555 · Cited by 68 · see citing works
HIV infection of non-classical cells in the brain
Wahl, A. R., & Al‐Harthi, L. (2023) · Retrovirology · doi:10.1186/s12977-023-00616-9 · Cited by 61 · see citing works
Type I astrocytes and microglia induce a cytokine response in an encephalitic murine coronavirus infection
Lavi, E., & Cong, L. (2020) · Experimental and Molecular Pathology · doi:10.1016/j.yexmp.2020.104474 · Cited by 59 · see citing works
Abnormal subpopulations of peripheral blood lymphocytes are involved in Parkinson’s disease
Sun, C., Zhao, Z., Yu, W., Mo, M., Song, C., Si, Y., & Liu, Y. (2019) · Annals of Translational Medicine · doi:10.21037/atm.2019.10.105 · Cited by 55 · see citing works
Unveiling the gut-brain axis: structural and functional analogies between the gut and the choroid plexus vascular and immune barriers
Carloni, S., & Rescigno, M. (2022) · Seminars in Immunopathology · doi:10.1007/s00281-022-00955-3 · Cited by 54 · see citing works
Cell-Mediated Immune Responses and Immunopathogenesis of Human Tick-Borne Encephalitis Virus-Infection
Blom, K. G., Cuapio, A., Sandberg, J. T., Varnaitė, R., Michaëlsson, J., Björkström, N. K., Sandberg, J. K., Klingström, J., Lindquist, L., Russ, S. G., et al. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02174 · Cited by 52 · see citing works
iNKT cells ameliorate human autoimmunity: Lessons from alopecia areata
Ghraieb, A., Keren, A., Ginzburg, A., Ullmann, Y., Schrum, A. G., Paus, R., & Gilhar, A. (2018) · Journal of Autoimmunity · doi:10.1016/j.jaut.2018.04.001 · Cited by 51 · see citing works
The features of the glymphatic system
Nycz, B., & Mandera, M. (2021) · Autonomic Neuroscience · doi:10.1016/j.autneu.2021.102774 · Cited by 49 · see citing works
The role of the CD8+ T cell compartment in ageing and neurodegenerative disorders
Terrabuio, E., Zenaro, E., & Constantin, G. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1233870 · Cited by 48 · see citing works
DAT and TH expression marks human Parkinson’s disease in peripheral immune cells
Gopinath, A., Mackie, P. M., Hashimi, B., Buchanan, A. M., Smith, A. R., Bouchard, R. S., Shaw, G., Badov, M., Saadatpour, L., Gittis, A. H., et al. (2022) · npj Parkinson s Disease · doi:10.1038/s41531-022-00333-8 · Cited by 45 · see citing works
Potential immunotherapies for traumatic brain and spinal cord injury
Putatunda, R., Bethea, J. R., & Hu, W.-H. (2018) · Chinese Journal of Traumatology · doi:10.1016/j.cjtee.2018.02.002 · Cited by 46 · see citing works
Immunosuppression by opioids: Mechanisms of action on innate and adaptive immunity
Sun, Q., Li, Z., Wang, Z., Wang, Q., Qin, F., Pan, H., Lin, W., Mu, X., Wang, Y., Jiang, Y., et al. (2023) · Biochemical Pharmacology · doi:10.1016/j.bcp.2023.115417 · Cited by 46 · see citing works
IL-33/ST2 Pathway and Galectin-3 as a New Analytes in Pathogenesis and Cardiometabolic Risk Evaluation in Psychosis
Borovčanin, M., Janicijevic, S. M., Jovanović, I., Gajović, N., Arsenijević, N., & Lukić, M. L. (2018) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2018.00271 · Cited by 45 · see citing works
Inflammation and Severe Cerebral Venous Thrombosis
Hu, S., Lee, H., Zhao, H., Ding, Y., & Duan, J. (2022) · Frontiers in Neurology · doi:10.3389/fneur.2022.873802 · Cited by 40 · see citing works
Meningeal immunity: Structure, function and a potential therapeutic target of neurodegenerative diseases
Ma, T., Wang, F., Xu, S., & Huang, J. H. (2021) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2021.01.028 · Cited by 37 · see citing works
Modeling glioblastoma complexity with organoids for personalized treatments
Pawlowski, K. D., Duffy, J. T., Babak, M. V., & Balyasnikova, I. V. (2023) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2023.01.002 · Cited by 39 · see citing works
The Impact of the Endocrine and Immunological Function of Adipose Tissue on Reproduction in Women with Obesity
Mączka, K., Stasiak, O., Przybysz, P., Grymowicz, M., & Smolarczyk, R. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25179391 · Cited by 38 · see citing works
Beneficial and Detrimental Effects of Regulatory T Cells in Neurotropic Virus Infections
Ciurkiewicz, M., Herder, V., & Beineke, A. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21051705 · Cited by 38 · see citing works
Landmark clinical observations and immunopathogenesis pathways linked to HIV and Cryptococcus fatal central nervous system co‐infection
Okurut, S., Boulware, D. R., Olobo, J. O., & Meya, D. B. (2020) · Mycoses · doi:10.1111/myc.13122 · Cited by 34 · see citing works
Phosphorylation of ERK-Dependent NF-κB Triggers NLRP3 Inflammasome Mediated by Vimentin in EV71-Infected Glioblastoma Cells
Gong, Z., Gao, X.-F., Yang, Q., Lun, J., Xiao, H., Zhong, J.-Y., & Cao, H. (2022) · Molecules · doi:10.3390/molecules27134190 · Cited by 32 · see citing works
Single-Cell RNA Sequencing Reveals the Diversity of the Immunological Landscape following Central Nervous System Infection by a Murine Coronavirus
Syage, A., Ekiz, H. A., Skinner, D. D., Stone, C., O'Connell, R., & Lane, T. (2020) · Journal of Virology · doi:10.1128/jvi.01295-20 · Cited by 31 · see citing works
Neuroimmunology of rabies: New insights into an ancient disease
Bastos, V., Pacheco, V., Rodrigues, É., Moraes, C. N. S., Nóbile, A., Fonseca, D., Souza, K. B. S., Vale, F. D., Filgueiras, I., Schimke, L. F., et al. (2023) · Journal of Medical Virology · doi:10.1002/jmv.29042 · Cited by 28 · see citing works
Genetic Alterations in Gliomas Remodel the Tumor Immune Microenvironment and Impact Immune-Mediated Therapies
Garcia-Fabiani, M. B., Haase, S., Comba, A., Carney, S. V., McClellan, B. L., Banerjee, K., Alghamri, M. S., Faisal, S. M., Kadiyala, P., Núñez, F. J., et al. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.631037 · Cited by 28 · see citing works
Combined cytotoxic and immune-stimulatory gene therapy using Ad-TK and Ad-Flt3L: Translational developments from rodents to glioma patients
Faisal, S. M., Castro, M. G., & Lowenstein, P. R. (2023) · Molecular Therapy · doi:10.1016/j.ymthe.2023.08.009 · Cited by 24 · see citing works
Contribution of Pro-Inflammatory Molecules Induced by Respiratory Virus Infections to Neurological Disorders
Böhmwald, K., Andrade, C. A., & Kalergis, A. M. (2021) · Pharmaceuticals · doi:10.3390/ph14040340 · Cited by 28 · see citing works
[Retracted] Glymphatic System: Emerging Therapeutic Target for Neurological Diseases
Xuan, X., Zhou, G., Chen, C., Shao, A., Zhou, Y., Li, X., & Zhou, J. (2022) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2022/6189170 · Cited by 24 · see citing works
Retracted
Immunotherapy for gliomas: shedding light on progress in preclinical and clinical development
Garcia-Fabiani, M. B., Ventosa, M., Comba, A., Candolfi, M., Candia, A. J. N., Alghamri, M. S., Kadiyala, P., Carney, S. V., Faisal, S. M., Schwendeman, A. A., et al. (2020) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2020.1768528 · Cited by 24 · see citing works
Infections in the Developing Brain: The Role of the Neuro-Immune Axis
Kim, J., Erice, C., Rohlwink, U. K., & Tucker, E. W. (2022) · Frontiers in Neurology · doi:10.3389/fneur.2022.805786 · Cited by 24 · see citing works
Dopamine–mediated immunomodulation affects choroid plexus function
Castellani, G., Contarini, G., Mereu, M., Albanesi, E., Devroye, C., D’Amore, C., Ferretti, V., Martin, S. D., & Papaleo, F. (2019) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2019.06.006 · Cited by 22 · see citing works
HIV-1 Myeloid Reservoirs — Contributors to Viral Persistence and Pathogenesis
Ferreira, E. A., Clements, J. E., & Veenhuis, R. T. (2024) · Current HIV/AIDS Reports · doi:10.1007/s11904-024-00692-2 · Cited by 20 · see citing works
Decoding intrathecal immunoglobulins and B cells in the CNS: their synthesis, function, and regulation
Negi, N., & Das, B. K. (2020) · International Reviews of Immunology · doi:10.1080/08830185.2019.1711073 · Cited by 20 · see citing works
Vascular Cognitive Impairment—The Molecular Basis and Potential Influence of the Gut Microbiota on the Pathological Process
Olejnik, P., & Golenia, A. (2024) · Cells · doi:10.3390/cells13231962 · Cited by 20 · see citing works
Reassessment of the blood-brain barrier: a potential target for viral entry into the immune-privileged brain
Stefano, G. B., Büttiker, P., & Kream, R. M. (2022) · GERMS · doi:10.18683/germs.2022.1310 · Cited by 18 · see citing works
The relationship between the serotonergic system and COVID-19 disease: A review
Eteraf-Oskouei, T., & Najafi, M. (2022) · Heliyon · doi:10.1016/j.heliyon.2022.e09544 · Cited by 18 · see citing works
The Interplay between Meningeal Lymphatic Vessels and Neuroinflammation in Neurodegenerative Diseases
Chen, J., Pan, Y., Liu, Q., Li, G., Chen, G., Li, W., Zhao, W., & Wang, Q. (2022) · Current Neuropharmacology · doi:10.2174/1570159x21666221115150253 · Cited by 18 · see citing works
Tolerogenic vaccines: Targeting the antigenic and cytokine niches of FOXP3+ regulatory T cells
Mannie, M. D., DeOca, K. B., Bastian, A. G., & Moorman, C. D. (2020) · Cellular Immunology · doi:10.1016/j.cellimm.2020.104173 · Cited by 17 · see citing works
Peripherally-sourced myeloid antigen presenting cells increase with advanced aging
Honarpisheh, P., Blixt, F. W., Conesa, M. P. B., Won, W. W., d’Aigle, J., Munshi, Y., Hudobenko, J., Furr, J. W., Mobley, A. S., Lee, J., et al. (2020) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2020.08.023 · Cited by 17 · see citing works
Combination of immunotherapy and radiotherapy in the treatment of brain metastases from non-small cell lung cancer
Suwiński, R. (2021) · Journal of Thoracic Disease · doi:10.21037/jtd-2019-rbmlc-08 · Cited by 17 · see citing works
The Involvement of Immune Cells Between Ischemic Stroke and Gut Microbiota
Pu, B., Zhu, H., Wei, L., Gu, L., Zhang, S., Jian, Z., & Xiong, X. (2023) · Translational Stroke Research · doi:10.1007/s12975-023-01151-7 · Cited by 16 · see citing works
Extracranial systemic antitumor response through the abscopal effect induced by brain radiation in a patient with metastatic melanoma
D’Andrea, M. A., & Reddy, G. K. (2019) · Radiation Oncology Journal · doi:10.3857/roj.2019.00437 · Cited by 16 · see citing works
Facing CAR T Cell Challenges on the Deadliest Paediatric Brain Tumours
Ferreras, C., Fernández, L., Villa, L. C., Ibáñez-Navarro, M., Martín-Cortázar, C., Esteban‐Rodríguez, I., Saceda-Gutierrez, J. M., & Pérez‐Martínez, A. (2021) · Cells · doi:10.3390/cells10112940 · Cited by 15 · see citing works
Importance of crosstalk between the microbiota and the neuroimmune system for tissue homeostasis
Li, K., Ly, K., Mehta, S. Y., & Braithwaite, A. W. (2022) · Clinical & Translational Immunology · doi:10.1002/cti2.1394 · Cited by 15 · see citing works
Targeting the tumor microenvironment in primary central nervous system lymphoma: Implications for prognosis
Shi, H., Sun, X., Wu, Y., Cui, Q., Sun, S., Ji, N., & Liu, Y. (2024) · Journal of Clinical Neuroscience · doi:10.1016/j.jocn.2024.04.009 · Cited by 14 · see citing works
An Update on the Clinical Status, Challenges, and Future Directions of Oncolytic Virotherapy for Malignant Gliomas
Stergiopoulos, G. M., Concilio, S. C., & Galanis, E. (2024) · Current Treatment Options in Oncology · doi:10.1007/s11864-024-01211-6 · Cited by 14 · see citing works
Crosstalk between neurokinin receptor signaling and neuroinflammation in neurological disorders
Eapen, P., Rao, C. M., & Nampoothiri, M. (2018) · Reviews in the Neurosciences · doi:10.1515/revneuro-2018-0021 · Cited by 14 · see citing works
In situ vaccination at a peripheral tumor site augments response against melanoma brain metastases
Clark, P. A., Sriramaneni, R. N., Jin, W. J., Jagodinsky, J. C., Bates, A. M., Jaquish, A. A., Anderson, B. R., Le, T. Q. H., Lubin, J. A., Chakravarty, I., et al. (2020) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2020-000809 · Cited by 14 · see citing works
Primary central nervous system Hodgkin Lymphoma: A case discussion and a hypothesis on the etiology
Alfaseh, A., Rajeh, N., & Hamed, G. (2018) · Avicenna Journal of Medicine · doi:10.4103/ajm.ajm_104_18 · Cited by 13 · see citing works
In this issue: Role of specific and non-specific immunity in disease
Kumar, H., & Bot, A. I. (2018) · International Reviews of Immunology · doi:10.1080/08830185.2018.1432192 · Cited by 13 · see citing works
Single-Cell Map of Diverse Immune Phenotypes in the Metastatic Brain Tumor Microenvironment of Non Small Cell Lung CancerPreprint
Wang, L., Dai, J., Han, R.-R., Dong, L., Feng, D., Zhu, G., Guo, W., Wang, Y., Chao, M., Jin, M., et al. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2019.12.30.890517 · Cited by 13 · see citing works
Transmigration across a Steady-State Blood–Brain Barrier Induces Activation of Circulating Dendritic Cells Partly Mediated by Actin Cytoskeletal Reorganization
Meena, M., Delen, M. V., Laere, M. D., Sterkens, A., Romero, C. C., Berneman, Z. N., & Cools, N. (2021) · Membranes · doi:10.3390/membranes11090700 · Cited by 12 · see citing works
Neutrophils in the Focus: Impact on Neuroimmune Dynamics and the Gut–Brain Axis
Kršek, A., & Batičić, L. (2024) · Gastrointestinal Disorders · doi:10.3390/gidisord6030039 · Cited by 12 · see citing works
Genetic dependency of Alzheimer’s disease-associated genes across cells and tissue types
Jaladanki, S. K., Elmas, A., Malavé, G. S., & Huang, K. (2021) · Scientific Reports · doi:10.1038/s41598-021-91713-2 · Cited by 10 · see citing works
Microglia-mediated inflammatory destruction of neuro-cardiovascular dysfunction after stroke
Deng, J., Chen, C., Xue, S., Su, D., Poon, W. S., Hou, H., & Wang, J. (2023) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2023.1117218 · Cited by 9 · see citing works
Overview of peripheral and central inflammatory responses and their contribution to neurotoxicity
Filipov, N. M. (2018) · Advances in neurotoxicology · doi:10.1016/bs.ant.2018.10.001 · Cited by 9 · see citing works
Extracranial Abscopal Effects Induced by Brain Radiation in Advanced Lung Cancer
D’Andrea, M. A., & Reddy, G. K. (2019) · American Journal of Clinical Oncology · doi:10.1097/coc.0000000000000623 · Cited by 9 · see citing works
An evaluation of the recognised systemic inflammatory biomarkers of chronic sub-optimal inflammation provides evidence for inflammageing (IFA) during multiple sclerosis (MS)
Bolton, C. (2021) · Immunity & Ageing · doi:10.1186/s12979-021-00225-0 · Cited by 10 · see citing works
H3.3-G34R Mutation-Mediated Epigenetic Reprogramming Leads to Enhanced Efficacy of Immune Stimulatory Gene Therapy in Diffuse Hemispheric GliomasPreprint
Garcia-Fabiani, M. B., Haase, S., Banerjee, K., Zhu, Z., McClellan, B. L., Mujeeb, A., Li, Y., Tronrud, C. E., Varela, M. L., West, M. E. J., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.06.13.544658 · Cited by 9 · see citing works
Efficacy and safety analysis on dendritic cell-based vaccine-treated high-grade glioma patients: a systematic review and meta-analysis
Li, C., Liu, T., Zhou, B., Zhou, Y., Yu, H., & Sun, Y. T. (2018) · OncoTargets and Therapy · doi:10.2147/ott.s177768 · Cited by 8 · see citing works
Primary central nervous system Hodgkin's lymphoma: a case report
Fu, H., Shi, S., Chen, L., Xu, B., Huang, W., Chen, Y., Wu, X., Shen, J., & Liu, T. (2021) · Journal of International Medical Research · doi:10.1177/0300060521999533 · Cited by 8 · see citing works
Molecular and Cellular Mechanisms of Neuroinflammation
Vito, A. D., Donato, G., & Tomassoni, D. (2017) · BioMed Research International · doi:10.1155/2017/8417183 · Cited by 8 · see citing works
CAR-T cell therapy in the treatment of relapsed or refractory primary central nervous system lymphoma: recent advances and challenges
Xiong, S., Zhang, S., Yue, N., Cao, J., & Wu, C. (2025) · Leukemia & lymphoma/Leukemia and lymphoma · doi:10.1080/10428194.2025.2458214 · Cited by 7 · see citing works
The Story Behind the First Mini-BEAM Photon Radiation Treatment: What is the Mini-Beam and Why is it Such an Advance?
Kundapur, V., Torlakovic, E., & Auer, R. N. (2024) · Seminars in Radiation Oncology · doi:10.1016/j.semradonc.2024.04.003 · Cited by 7 · see citing works
Immune Privileges as a Result of Mutual Regulation of Immune and Stem Systems
Karpenko, D. V. (2023) · Biochemistry (Moscow) · doi:10.1134/s0006297923110123 · Cited by 7 · see citing works
Allogeneic Blood or Marrow Transplantation with Nonmyeloablative Conditioning and High-Dose Cyclophosphamide-Based Graft-versus-Host Disease Prophylaxis for Secondary Central Nervous System Lymphoma
Sterling, C. H., Tsai, H., Holdhoff, M., Bolaños‐Meade, J., Luznik, L., Fuchs, E. J., Huff, C. A., Gocke, C. B., Ali, S. A., Borrello, I., et al. (2021) · Transplantation and Cellular Therapy · doi:10.1016/j.jtct.2021.07.015 · Cited by 7 · see citing works
Serum Proteomics Identified TAFI as a Potential Molecule Facilitating the Migration of Peripheral Monocytes to Damaged White Matter During Chronic Cerebral Hypoperfusion
Wang, Y., Cheng, W., Chen, X., Cheng, C., Zhang, L., & Huang, W. C. (2023) · Neurochemical Research · doi:10.1007/s11064-023-04050-3 · Cited by 6 · see citing works
Inflammatory Astrocytic TGFβ Signaling Induced by Blood–Brain Barrier Dysfunction Drives Epileptogenesis
Yang, L. T., Anthony, G., & Kaufer, D. (2024) · doi:10.1093/med/9780197549469.003.0028 · Cited by 6 · see citing works
Arsenic Exposure Induces Neuro-immune Toxicity in the Cerebral Cortex and the Hippocampus via Neuroglia and NLRP3 Inflammasome Activation in C57BL/6 Mice
Yan, N., Wang, Z., Li, Z., Zheng, Y., Chang, N., Xu, K., Wang, Q., & Duan, X. (2023) · Biological Trace Element Research · doi:10.1007/s12011-023-04012-4 · Cited by 6 · see citing works
Major Differences in Lymphocyte Subpopulations Between Cerebrospinal Fluid and Peripheral Blood in Non-Hodgkin Lymphoma Without Leptomeningeal Involvement: Flow Cytometry Evidence of a Cerebral Lymphatic System
Cordone, I., Masi, S., Giannarelli, D., Pasquale, A., Conti, L., Telera, S. M., Pace, A., Papa, E., Marino, M., de Fabritiis, P., et al. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.685786 · Cited by 6 · see citing works
Extrinsic factors associated with the response to immunotherapy in glioblastoma
Bi, H., & Zhang, C. (2021) · Cancer Letters · doi:10.1016/j.canlet.2021.04.018 · Cited by 5 · see citing works
Multiple Sclerosis as a Syndrome—Implications for Future Management
Dwyer, C., Nguyen, L. T.-T., Healy, L. M., Dutta, R., Ludwin, S. K., Antel, J. P., Binder, M. D., & Kilpatrick, T. J. (2020) · Frontiers in Neurology · doi:10.3389/fneur.2020.00784 · Cited by 5 · see citing works
Brain Radiation Induced Extracranial Abscopal Effects in Metastatic Melanoma
D’Andrea, M. A., & Reddy, G. K. (2020) · American Journal of Clinical Oncology · doi:10.1097/coc.0000000000000760 · Cited by 5 · see citing works
Interaction of maternal immune activation and genetic interneuronal inhibition
Anderson, A. C., Genaro‐Mattos, T. C., Allen, L. B., Koczok, K., Korade, Ž., & Mirnics, K. (2021) · Brain Research · doi:10.1016/j.brainres.2021.147370 · Cited by 5 · see citing works
Intra-nasal administration of sperm head turns neutrophil into reparative mode after PGE1- and/or Ang II receptor-mediated phagocytosis followed by expression of sperm head’s coding RNA
Pakravan, N., Hassan, Z. M., & Abbasi, A. (2021) · International Immunopharmacology · doi:10.1016/j.intimp.2021.107696 · Cited by 5 · see citing works
Title: Immunotherapy; a ground-breaking remedy for spinal cord injury with stumbling blocks: An overview
Saeed, Y. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1110008 · Cited by 4 · see citing works
The Roles of T Cells in Clinical Depression
Toben, C. G., & Baune, B. T. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-811073-7.00007-6 · Cited by 4 · see citing works
Clinical utility of CAR T cell therapy in brain tumors: Lessons learned from the past, current evidence and the future stakes
Chatterjee, A., Asija, S., Yadav, S., Purwar, R., & Goda, J. S. (2022) · International Reviews of Immunology · doi:10.1080/08830185.2022.2125963 · Cited by 3 · see citing works
Innate Immunity and Parkinson's DiseasePreprint
Oludipe, D. B., Du, X., Akter, S., Zhang, C., Mosley, R. L., Gendelman, H. E., & Sil, S. (2025) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a041640 · Cited by 3 · see citing works
Neuroprotective Immunity for Neurodegenerative and Neuroinfectious Diseases
Olson, K. E., Mosley, R. L., & Gendelman, H. E. (2020) · Springer eBooks · doi:10.1007/978-3-030-33946-3_8 · Cited by 2 · see citing works
Interaction between Gut Microbiota and Central and Enteric Nervous Systems: The Gut–Brain Axis Concept
Arbab, M. H. (2023) · doi:10.1002/9781119904786.ch15 · Cited by 2 · see citing works
The Mediterranean sea bass Dicentrarchus labrax: A marine model species in fish immunology
Picchietti, S., Pianese, V., Fausto, A. M., & Scapigliati, G. (2025) · Fish & Shellfish Immunology · doi:10.1016/j.fsi.2025.110288 · Cited by 1 · see citing works
The Gut Vascular Barrier: Linking the Intestinal Environment with Blood Circulation
Carloni, S., & Strati, F. (2025) · The microbiomes of humans, animals, plants, and the environment · doi:10.1007/978-3-031-84065-4_4 · Cited by 1 · see citing works
Toll like receptor 4 (TLR4) in neuroinflammation: From acute hemorrhagic stroke to chronic neurodegeneration
Choudhary, H. H., Yoshida, J., Islam, R., Wang, Z., & Hanafy, K. A. (2026) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x261468877 · Cited by 1 · see citing works
Effects of Stress on the Brain’s Glymphatic System
Ivanovska, M., Naimova, M., & Murdjeva, M. (2023) · South East European Journal of Immunology · doi:10.3889/seejim.2023.6040 · Cited by 1 · see citing works
Glucan Coated Iron Oxide Nanoparticles for Regulating Survival, Inflammation and Oxidative Stress in Parkinsons Disease
Zhu, L., Feng, L., Ma, D., Zhao, L., Hao, Y., Wang, X., Nan, D., Feng, J., & Zhang, Y. (2023) · Journal of Biomedical Nanotechnology · doi:10.1166/jbn.2023.3658 · Cited by 1 · see citing works

Basic principles of neuroimmunology
Yoshida, T. M., Wang, A., & Hafler, D. A. (2022) · Seminars in Immunopathology · doi:10.1007/s00281-022-00951-7 · Cited by 24 · see citing works
Beyond immune privilege: the brain as a dynamic immunological interface
Kobeissy, F. H., & Salzet, M. (2026) · Cell Death and Disease · doi:10.1038/s41419-026-08561-z · Cited by 9 · see citing works
The Immune System of the Brain
Jones, T. B., Lucin, K. M., & Popovich, P. G. (2007) · Neuroimmune biology · doi:10.1016/s1567-7443(07)00207-4 · Cited by 5 · see citing works
Revisiting the Mechanisms of CNS Immune Privilege
Louveau, A., Harris, T. H., & Kipnis, J. (2015) · Trends in Immunology · doi:10.1016/j.it.2015.08.006 · Cited by 682 · see citing works
Is Central Nervous System an Immune-Privileged Site?
Shrestha, R., Millington, O. R., Brewer, J. M., & Bushell, T. J. (2014) · Kathmandu University Medical Journal · doi:10.3126/kumj.v11i1.11055 · Cited by 26 · see citing works

Authors: Negi, N., & Das, B. K.
Affiliations: Umeå University (SE)
All India Institute of Medical Sciences (IN)
Corresponding author: Das, Bimal K.
ORCID: Negi, Neema
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
DOI: 10.1080/08830185.2017.1357719
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
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › 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

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.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

CNS: Not an immunoprivilaged site anymore but a virtual secondary lymphoid organ

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Cites

Cited by

Related

Record

About these checks