IFN-γ-dependent activation of the brain’s choroid plexus for CNS immune surveillance and repair
Abstract
Infiltrating T cells and monocyte-derived macrophages support central nervous system repair. Although infiltration of leucocytes to the injured central nervous system has recently been shown to be orchestrated by the brain's choroid plexus, the immunological mechanism that maintains this barrier and regulates its activity as a selective gate is poorly understood. Here, we hypothesized that CD4(+) effector memory T cells, recently shown to reside at the choroid plexus stroma, regulate leucocyte trafficking through this portal through their interactions with the choroid plexus epithelium. We found that the naïve choroid plexus is populated by T helper 1, T helper 2 and regulatory T cells, but not by encephalitogenic T cells. In vitro findings revealed that the expression of immune cell trafficking determinants by the choroid plexus epithelium is specifically induced by interferon-γ. Tumour necrosis factor-α and interferon-γ reciprocally controlled the expression of their receptors by the choroid plexus epithelium, and had a synergistic effect in inducing the epithelial expression of trafficking molecules. In vivo, interferon-γ-dependent signalling controlled trafficking through the choroid plexus; interferon-γ receptor knockout mice exhibited reduced levels of T cells and monocyte entry to the cerebrospinal fluid and impaired recovery following spinal cord injury. Moreover, reduced expression of trafficking molecules by the choroid plexus was correlated with reduced CD4(+) T cells in the choroid plexus and cerebrospinal fluid of interferon-γ receptor knockout mice. Similar effect on the expression of trafficking molecules by the choroid plexus was found in bone-marrow chimeric mice lacking interferon-γ receptor in the central nervous system, or reciprocally, lacking interferon-γ in the circulation. Collectively, our findings attribute a novel immunological plasticity to the choroid plexus epithelium, allowing it to serve, through interferon-γ signalling, as a tightly regulated entry gate into the central nervous system for circulating leucocytes immune surveillance under physiological conditions, and for repair following acute injury.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
In a spinal cord injury mouse model, knockout of IFN-γ receptor reduces infiltration of T cells and monocytes to the CSF, impairs resolution of inflammation, and attenuates recovery.
“In spinal cord injury mouse model, knockout of IFN-γ receptor reduced the infiltration of T cells and monocytes to the CSF, impaired the resolution of inflammation and attenuated recovery.”
From Role of neuroinflammation in neurodegeneration development (2023) · cites this paper as [147]
IFN-γ is crucial for the expression of resolving macrophage attracting factors by the choroid plexus epithelium.
“IFN-γ was verified as the crucial player in the expression of resolving macrophages attracting factors by the choroid plexus epithelium.”
From Role of neuroinflammation in neurodegeneration development (2023) · cites this paper as [147]
TNF-α and IFN-γ reciprocally control the expression of their receptors in the choroid plexus, through which they synergistically activate the choroid plexus epithelium to express trafficking molecules.
“Immunostaining of the in vitro cell culture and the choroid plexus from mice revealed that TNF-α and IFN-γ reciprocally control the expression of their receptors in the choroid plexus, through which way they synergistically activate the choroid plexus epithelium to express trafficking molecules.”
From Role of neuroinflammation in neurodegeneration development (2023) · cites this paper as [147]
Cites
The chemokine system in diverse forms of macrophage activation and polarization
MANTOVANI, A., SICA, A., SOZZANI, S., ALLAVENA, P., VECCHI, A., & LOCATI, M. (2004) · Trends in Immunology · doi:10.1016/j.it.2004.09.015 · Cited by 6,534 · see citing works
Alternative activation of macrophages
Gordon, S. (2003) · Nature Reviews Immunology · doi:10.1038/nri978 · Cited by 6,189 · see citing works
Korn, T., Bettelli, E., Oukka, M., & Kuchroo, V. K. (2009) · Annual Review of Immunology · doi:10.1146/annurev.immunol.021908.132710 · Cited by 4,873 · see citing works
Jung, S., Aliberti, J., Graemmel, P., Sunshine, M. J., Kreutzberg, G. W., Sher, A., & Littman, D. R. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.11.4106-4114.2000 · Cited by 2,632 · see citing works
Regulatory T Cell Lineage Specification by the Forkhead Transcription Factor Foxp3
Fontenot, J. D., Rasmussen, J. P., Williams, L. M., Dooley, J., Farr, A. G., & Rudensky, A. Y. (2005) · Immunity · doi:10.1016/j.immuni.2005.01.016 · Cited by 2,255 · see citing works
Basso, D., Fisher, L., Anderson, A., Jakeman, L., McTigue, D. M., & Popovich, P. (2006) · Journal of Neurotrauma · doi:10.1089/neu.2006.23.635 · Cited by 1,615 · see citing works
Simard, A. R., Soulet, D., Gowing, G., Julien, J.-P., & Rivest, S. (2006) · Neuron · doi:10.1016/j.neuron.2006.01.022 · Cited by 1,265 · see citing works
Reboldi, A., Coisne, C., Baumjohann, D., Benvenuto, F., Bottinelli, D., Lira, S., Uccelli, A., Lanzavecchia, A., Engelhardt, B., & Sallusto, F. (2009) · Nature Immunology · doi:10.1038/ni.1716 · Cited by 1,206 · see citing works
Codarri, L., Gyülvészi, G., Tosevski, V., Hesske, L., Fontana, A., Magnenat, L., Suter, T., & Becher, B. (2011) · Nature Immunology · doi:10.1038/ni.2027 · Cited by 1,191 · cited 2× · see citing works
“Granulocyte-macrophage colony-stimulating factor (GM-CSF) secreting helper T cells were shown to be highly ence- phalitogenic (Codarri et al., 2011), we therefore also examined whether this cell population is present in the choroid plexus, and found it to be absent in the naı̈ve choroid plexus…”
BackgroundAutoimmune T cells protect neurons from secondary degeneration after central nervous system axotomy
Moalem‐Taylor, G., Leibowitz‐Amit, R., Yoles, E., Mor, F., Cohen, I. R., & Schwartz, M. (1999) · Nature Medicine · doi:10.1038/4734 · Cited by 882 · see citing works
Self-citationShechter, R., London, A., Varol, C., Raposo, C., Cusimano, M., Yovel, G., Rolls, A., Mack, M., Pluchino, S., Martino, G., et al. (2009) · PLoS Medicine · doi:10.1371/journal.pmed.1000113 · Cited by 770 · see citing works
Self-citationShechter, R., Miller, O., Yovel, G., Rosenzweig, N., London, A., Ruckh, J., Kim, K.-W., Klein, E., Kalchenko, V., Bendel, P., et al. (2013) · Immunity · doi:10.1016/j.immuni.2013.02.012 · Cited by 683 · see citing works
Self-citationBurgess, A., Vigneron, S., Brioudes, E., Labbé, J., Lorca, T., & Castro, A. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0914191107 · Cited by 681 · see citing works
D'Mello, C., Le, T., & Swain, M. G. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.3567-08.2009 · Cited by 675 · see citing works
The ins and outs of T-lymphocyte trafficking to the CNS: anatomical sites and molecular mechanisms
Engelhardt, B., & Ransohoff, R. M. (2005) · Trends in Immunology · doi:10.1016/j.it.2005.07.004 · Cited by 674 · see citing works
Wild-type microglia arrest pathology in a mouse model of Rett syndrome
Derecki, N. C., Cronk, J. C., Lu, Z., Xu, E., Abbott, S. B. G., Guyenet, P. G., & Kipnis, J. (2012) · Nature · doi:10.1038/nature10907 · Cited by 607 · see citing works
Pineau, I., & Lacroix, S. (2006) · The Journal of Comparative Neurology · doi:10.1002/cne.21149 · Cited by 592 · see citing works
Kivisäkk, P., Mahad, D., Callahan, M. K., Trebst, C., Tucky, B. H., Wei, T., Wu, L., Bækkevold, E. S., Lassmann, H., Staugaitis, S. M., et al. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1433000100 · Cited by 546 · 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
IL-4-Induced Arginase 1 Suppresses Alloreactive T Cells in Tumor-Bearing Mice
Bronte, V., Serafini, P., Santo, C. D., Marigo, I., Tosello, V., Mazzoni, A., Segal, D. M., Staib, C., Löwel, M., Sutter, G., et al. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.170.1.270 · Cited by 513 · see citing works
Beers, D. R., Henkel-Tigges, J., Zhao, W., Wang, J., & Appel, S. H. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0807419105 · Cited by 468 · see citing works
Analysis of Type 2 Immunity In Vivo with a Bicistronic IL-4 Reporter
Mohrs, M., Shinkai, K., Mohrs, K., & Locksley, R. M. (2001) · Immunity · doi:10.1016/s1074-7613(01)00186-8 · Cited by 460 · see citing works
Hauben, E., Butovsky, O., Nevo, U., Yoles, E., Moalem‐Taylor, G., Agranov, E., Mor, F., Leibowitz‐Amit, R., Pevsner, E., AKSELROD, S., et al. (2000) · Journal of Neuroscience · doi:10.1523/jneurosci.20-17-06421.2000 · Cited by 367 · see citing works
Self-citationTwo Different Cell Types have Different Major Receptors for Human Tumor Necrosis Factor (TNFα)
Hohmann, H., Remy, R., Brockhaus, M., & van Loon, A. P. G. M. (1989) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)63791-3 · Cited by 351 · see citing works
Baruch, K., Ron‐Harel, N., Gal, H., Deczkowska, A., Shifrut, E., Ndifon, W. O., Mirlas-Neisberg, N., Cardon, M., Vaknin, I., Cahalon, L., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1211270110 · Cited by 296 · see citing works
Self-citationZiv, Y., Avidan, H., Pluchino, S., Martino, G., & Schwartz, M. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0603747103 · Cited by 285 · see citing works
Self-citationEngelhardt, B., & Coisne, C. (2011) · Fluids and Barriers of the CNS · doi:10.1186/2045-8118-8-4 · Cited by 248 · see citing works
Steffen, B. J., Breier, G., Butcher, E. C., Schulz, M., & Engelhardt, B. (1996) · Europe PMC (PubMed Central) · Cited by 245 · see citing works
The roles of TNF in brain dysfunction and disease
Clark, I. A., Alleva, L. M., & Vissel, B. (2010) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2010.08.007 · Cited by 232 · see citing works
Trivedi, A. A., Olivas, A. D., & Noble‐Haeusslein, L. J. (2006) · Clinical Neuroscience Research · doi:10.1016/j.cnr.2006.09.007 · Cited by 205 · see citing works
Adaptive Immune Neuroprotection in G93A-SOD1 Amyotrophic Lateral Sclerosis Mice
Banerjee, R., Mosley, R. L., Reynolds, A. D., Dhar, A., Jackson-Lewis, V. R., Gordon, P. H., Przedborski, S., & Gendelman, H. E. (2008) · PLoS ONE · doi:10.1371/journal.pone.0002740 · Cited by 198 · see citing works
CNS-specific T cells shape brain function via the choroid plexus
Baruch, K., & Schwartz, M. (2013) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2013.04.002 · Cited by 195 · see citing works
Self-citationShulman, Z., Cohen, S. J., Roediger, B., Kalchenko, V., Jain, R., Grabovsky, V., Klein, E., Shinder, V., Stoler‐Barak, L., Feigelson, S. W., et al. (2011) · Nature Immunology · doi:10.1038/ni.2173 · Cited by 174 · see citing works
Regional CNS responses to IFN-γ determine lesion localization patterns during EAE pathogenesis
Lees, J. R., Golumbek, P. T., Sim, J. E., Dorsey, D. A., & Russell, J. H. (2008) · The Journal of Experimental Medicine · doi:10.1084/jem.20080155 · Cited by 163 · see citing works
Synergistic effects of interferon γ and tumour necrosis factor α on T84 cell function
Fish, S. M., Proujansky, R., & Reenstra, W. W. (1999) · Gut · doi:10.1136/gut.45.2.191 · Cited by 161 · see citing works
Kivisäkk, P., Trebst, C., Liu, Z., Tucky, B. H., Sørensen, T. L., Rudick, R. A., Mack, M., & Ransohoff, R. M. (2002) · Clinical & Experimental Immunology · doi:10.1046/j.1365-2249.2002.01947.x · Cited by 142 · see citing works
Leukocyte–epithelial interactions
Zen, K., & Parkos, C. A. (2003) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(03)00103-0 · Cited by 135 · see citing works
Posttraumatic Invasion of Monocytes across the Blood—Cerebrospinal Fluid Barrier
Szmydynger-Chodobska, J., Strazielle, N., Gandy, J., Keefe, T. H., Zink, B., Ghersi-Egea, J., & Chodobski, A. (2012) · Journal of Cerebral Blood Flow and Metabolism · doi:10.1038/jcbfm.2011.111 · Cited by 129 · see citing works
Reducing post-traumatic anxiety by immunization
Lewitus, G. M., Cohen, H., & Schwartz, M. (2008) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2008.05.002 · Cited by 123 · see citing works
Self-citationVerotoxins induce apoptosis in human renal tubular epithelium derived cells
Taguchi, T., Uchida, H., Kiyokawa, N., Mori, T., Sato, N., Horie, H., Takeda, T., & Fujimoto, J. (1998) · Kidney International · doi:10.1046/j.1523-1755.1998.00939.x · Cited by 111 · see citing works
Ultrastructural localization of adhesion molecules in the healthy
Wolburg‐Buchholz, K., Gerhardt, H., Schulz, M., Wolburg, H., & Engelhardt, B. (1999) · Cell and Tissue Research · doi:10.1007/s004410051287 · Cited by 87 · see citing works
Kennedy, J. D., Hatfield, C. A., Fidler, S. F., Winterrowd, G. E., Haas, J. V., Chin, J. E., & Richards, I. M. (1995) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/ajrcmb.12.6.7766426 · Cited by 65 · see citing works
Ransohoff, R. M. (2009) · Nature · doi:10.1038/462041a · Cited by 63 · see citing works
Vaknin, I., Kunis, G., Miller, O., Butovsky, O., Bukshpan, S., Beers, D. R., Henkel, J. S., Yoles, E., Appel, S., & Schwartz, M. (2011) · PLoS ONE · doi:10.1371/journal.pone.0026921 · Cited by 62 · see citing works
Self-citationPetito, C. K., & Adkins, B. (2005) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2004.12.020 · Cited by 56 · see citing works
Epithelial ICAM‐1 and ICAM‐2 regulate the egression of human T cells across the bronchial epithelium
Porter, J. C., & Hall, A. (2008) · The FASEB Journal · doi:10.1096/fj.08-115899 · Cited by 55 · see citing works
Murugesan, N., Paul, D., Lemire, Y., Shrestha, B., Ge, S., & Pachter, J. S. (2012) · Fluids and Barriers of the CNS · doi:10.1186/2045-8118-9-15 · Cited by 47 · see citing works
Shedding of Tumor Necrosis Factor Type 1 Receptor after Experimental Spinal Cord Injury
Harrington, J. F., Messier, A. A., Levin, A. R., Szmydynger‐Chodobska, J., & Chodobski, A. (2005) · Journal of Neurotrauma · doi:10.1089/neu.2005.22.919 · Cited by 44 · see citing works
Silica-induced chemokine expression in alveolar type II cells is mediated by TNF-α
Barrett, E. G., Johnston, C. J., Oberdörster, G., & Finkelstein, J. N. (1998) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.1998.275.6.l1110 · Cited by 42 · see citing works
Microglial inhibitory factor (MIF/TKP) mitigates secondary damage following spinal cord injury
Emmetsberger, J., & Tsirka, S. E. (2012) · Neurobiology of Disease · doi:10.1016/j.nbd.2012.05.001 · Cited by 37 · see citing works
Porter, J. C., Falzon, M., & Hall, A. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.180.3.1866 · Cited by 36 · see citing works
Schwerk, C., Rybarczyk, K., Eßmann, F., Seibt, A., Mölleken, M.-L., Zeni, P., Schroten, H., & Tenenbaum, T. (2010) · BioMed Research International · doi:10.1155/2010/307231 · Cited by 35 · see citing works
Schwartz, M., & Baruch, K. (2012) · Human Vaccines & Immunotherapeutics · doi:10.4161/hv.21649 · Cited by 22 · see citing works
Self-citationHarm or heal – divergent effects of autoimmune neuroinflammation?
Olsson, T. P. (2002) · Trends in Immunology · doi:10.1016/s1471-4906(02)00003-0 · Cited by 17 · see citing works
Miller, L. A., & Butcher, E. C. (1998) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/ajrcmb.19.6.3245mrev · Cited by 17 · see citing works
Flagged first, then by citations
1 of the 57 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Role of neuroinflammation in neurodegeneration development
Zhang, W., Xiao, D., Mao, Q., & Xia, H. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01486-5 · Cited by 1,668 · see citing works
Origin, fate and dynamics of macrophages at central nervous system interfaces
Goldmann, T., Wieghofer, P., Jordão, M. J. C., Prutek, F., Hagemeyer, N., Frenzel, K., Amann, L., Staszewski, O., Kierdorf, K., Krueger, M., et al. (2016) · Nature Immunology · doi:10.1038/ni.3423 · Cited by 1,209 · see citing works
Unexpected role of interferon-γ in regulating neuronal connectivity and social behaviour
Filiano, A. J., Xu, Y., Tustison, N. J., Marsh, R. L., Baker, W., Smirnov, I., Overall, C. C., Gadani, S. P., Turner, S. D., Weng, Z., et al. (2016) · Nature · doi:10.1038/nature18626 · Cited by 697 · see citing works
Development and functions of the choroid plexus–cerebrospinal fluid system
Lun, M. P., Monuki, E. S., & Lehtinen, M. K. (2015) · Nature reviews. Neuroscience · doi:10.1038/nrn3921 · Cited by 682 · see citing works
Aging-induced type I interferon response at the choroid plexus negatively affects brain function
Baruch, K., Deczkowska, A., David, E., Castellano, J. M., Miller, O., Kertser, A., Berkutzki, T., Barnett-Itzhaki, Z., Bezalel, D., Wyss-Coray, T., et al. (2014) · Science · doi:10.1126/science.1252945 · Cited by 615 · see citing works
Self-citationThe microbiome: a key regulator of stress and neuroinflammation
Rea, K., Dinan, T. G., & Cryan, J. F. (2016) · Neurobiology of Stress · doi:10.1016/j.ynstr.2016.03.001 · Cited by 508 · see citing works
Baruch, K., Rosenzweig, N., Kertser, A., Deczkowska, A., Sharif, A. M., Spinrad, A., Tsitsou-Kampeli, A., Sarel, A., Cahalon, L., & Schwartz, M. (2015) · Nature Communications · doi:10.1038/ncomms8967 · Cited by 491 · see citing works
Self-citationRegulation of astrocyte activation by glycolipids drives chronic CNS inflammation
Mayo, L., Trauger, S. A., Blain, M., Nadeau, M., Patel, B., Alvarez, J. I., Mascanfroni, I. D., Yeste, A., Kivisäkk, P., Kallas, K., et al. (2014) · Nature Medicine · doi:10.1038/nm.3681 · Cited by 472 · see citing works
Contributions of Age-Related Thymic Involution to Immunosenescence and Inflammaging
Thomas, R., Wang, W., & Su, D.-M. (2020) · Immunity & Ageing · doi:10.1186/s12979-020-0173-8 · Cited by 442 · see citing works
Ghersi-Egea, J.-F., Strazielle, N., Catala, M., Silva-Vargas, V., Doetsch, F., & Engelhardt, B. (2018) · Acta Neuropathologica · doi:10.1007/s00401-018-1807-1 · Cited by 436 · see citing works
Baruch, K., Deczkowska, A., Rosenzweig, N., Tsitsou-Kampeli, A., Sharif, A. M., Matcovitch-Natan, O., Kertser, A., David, E., Amit, I., & Schwartz, M. (2016) · Nature Medicine · doi:10.1038/nm.4022 · Cited by 425 · see citing works
Self-citationImmune cell regulation of glia during CNS injury and disease
Greenhalgh, A. D., David, S., & Bennett, F. C. (2020) · Nature reviews. Neuroscience · doi:10.1038/s41583-020-0263-9 · Cited by 398 · see citing works
Transforming the understanding of brain immunity
Castellani, G., Croese, T., Peralta Ramos, J. M., & Schwartz, M. (2023) · Science · doi:10.1126/science.abo7649 · Cited by 386 · see citing works
Self-citationGadhave, D. G., Sugandhi, V. V., Jha, S. K., Nangare, S., Gupta, G., Singh, S. K., Dua, K., Cho, H., Hansbro, P. M., & Paudel, K. R. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102357 · Cited by 391 · see citing works
Choroid plexus and the blood–cerebrospinal fluid barrier in disease
Solár, P., Zamani, A., Kubíčková, L., Dubový, P., & Joukal, M. (2020) · Fluids and Barriers of the CNS · doi:10.1186/s12987-020-00196-2 · Cited by 365 · see citing works
Schwartz, M., & Baruch, K. (2014) · The EMBO Journal · doi:10.1002/embj.201386609 · Cited by 349 · see citing works
Self-citationThe anatomy and immunology of vasculature in the central nervous system
Mastorakos, P., & McGavern, D. (2019) · Science Immunology · doi:10.1126/sciimmunol.aav0492 · Cited by 333 · see citing works
Neurogenesis and Inflammation after Ischemic Stroke: What is Known and Where We Go from Here
Tobin, M. K., Bonds, J. A., Minshall, R. D., Pelligrino, D. A., Testai, F. D., & Lazarov, O. (2014) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2014.130 · Cited by 327 · see citing works
Signaling by cGAS–STING in Neurodegeneration, Neuroinflammation, and Aging
Paul, B. D., Snyder, S. H., & Bohr, V. A. (2020) · Trends in Neurosciences · doi:10.1016/j.tins.2020.10.008 · Cited by 324 · see citing works
Depression's Unholy Trinity: Dysregulated Stress, Immunity, and the Microbiome
Cruz-Pereira, J. S., Rea, K., Nolan, Y. M., O'Leary, O. F., Dinan, T. G., & Cryan, J. F. (2020) · Annual Review of Psychology · doi:10.1146/annurev-psych-122216-011613 · Cited by 320 · see citing works
The dual roles of cytokines in Alzheimer’s disease: update on interleukins, TNF-α, TGF-β and IFN-γ
Zheng, C., Zhou, X.-W., & Wang, J.-Z. (2016) · Translational Neurodegeneration · doi:10.1186/s40035-016-0054-4 · Cited by 292 · see citing works
Macrophage subsets and microglia in multiple sclerosis
Bogie, J. F. J., Stinissen, P., & Hendriks, J. J. A. (2014) · Acta Neuropathologica · doi:10.1007/s00401-014-1310-2 · Cited by 279 · see citing works
Identification of a choroid plexus vascular barrier closing during intestinal inflammation
Carloni, S., Bertocchi, A., Mancinelli, S., Bellini, M., Erreni, M., Borreca, A., Braga, D., Giugliano, S., Mozzarelli, A. M., Manganaro, D., et al. (2021) · Science · doi:10.1126/science.abc6108 · Cited by 272 · see citing works
Cytokines in CAR T Cell–Associated Neurotoxicity
Gust, J., Ponce, R. A., Liles, W. C., Garden, G. A., & Turtle, C. J. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.577027 · Cited by 268 · see citing works
How Do Immune Cells Support and Shape the Brain in Health, Disease, and Aging?
Schwartz, M., Kipnis, J., Rivest, S., & Prat, A. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.3241-13.2013 · Cited by 256 · see citing works
Self-citationBrain 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
Neurological Disease as a Failure of Brain-Immune Crosstalk: The Multiple Faces of Neuroinflammation
Schwartz, M., & Deczkowska, A. (2016) · Trends in Immunology · doi:10.1016/j.it.2016.08.001 · Cited by 246 · see citing works
Self-citationThe role of T cells in age-related diseases
Carrasco, E., Heras, M. M. G. D. L., Gabandé‐Rodríguez, E., Desdín-Micó, G., Aranda, J. F., & Mittelbrunn, M. (2021) · Nature reviews. Immunology · doi:10.1038/s41577-021-00557-4 · Cited by 244 · see citing works
Ionizing Radiation-Induced Immune and Inflammatory Reactions in the Brain
Lumniczky, K., Szatmári, T., & Sáfrány, G. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.00517 · Cited by 228 · see citing works
Rosenzweig, N., Dvir-Szternfeld, R., Tsitsou-Kampeli, A., Keren‐Shaul, H., Ben-Yehuda, H., Weill-Raynal, P., Cahalon, L., Kertser, A., Baruch, K., Amit, I., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-08352-5 · Cited by 224 · see citing works
Self-citationvan Langelaar, J., de Vries, R. M. V. D. V., Janssen, M., Wierenga‐Wolf, A. F., Spilt, I. M., Siepman, T. A. M., Dankers, W., Verjans, G. M. G. M., de Vries, H. E., Lubberts, E., et al. (2018) · Brain · doi:10.1093/brain/awy069 · Cited by 224 · see citing works
Drowning stars: reassessing the role of astrocytes in brain edema
Thrane, A. S., Thrane, V. R., & Nedergaard, M. (2014) · Trends in Neurosciences · doi:10.1016/j.tins.2014.08.010 · Cited by 218 · see citing works
Peripheral immune system in aging and Alzheimer’s disease
Cao, W., & Zheng, H. (2018) · Molecular Neurodegeneration · doi:10.1186/s13024-018-0284-2 · Cited by 214 · see citing works
Taggart, D., Andreou, T., Scott, K. J., Williams, J. M., Rippaus, N., Brownlie, R. J., Ilett, E. J., Salmond, R. J., Melcher, A. A., & Lorger, M. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1714089115 · Cited by 209 · see citing works
Neural stem cell therapy for subacute and chronic ischemic stroke
Boese, A. C., Le, Q.-S. E., Pham, D., Hamblin, M. H., & Lee, J.-P. (2018) · Stem Cell Research & Therapy · doi:10.1186/s13287-018-0913-2 · Cited by 205 · see citing works
Regeneration of Spinal Cord Connectivity Through Stem Cell Transplantation and Biomaterial Scaffolds
Katoh, H., Yokota, K., & Fehlings, M. G. (2019) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2019.00248 · Cited by 199 · see citing works
Immune Surveillance of the CNS following Infection and Injury
Russo, M. V., & McGavern, D. B. (2015) · Trends in Immunology · doi:10.1016/j.it.2015.08.002 · Cited by 191 · see citing works
Immune cell compartmentalization for brain surveillance and protection
Croese, T., Castellani, G., & Schwartz, M. (2021) · Nature Immunology · doi:10.1038/s41590-021-00994-2 · Cited by 188 · see citing works
Self-citationRicigliano, V. A. G., Morena, E., Colombi, A., Tonietto, M., Hamzaoui, M., Poirion, É., Bottlaender, M., Gervais, P., Louapre, C., Bodini, B., et al. (2021) · Radiology · doi:10.1148/radiol.2021204426 · Cited by 188 · see citing works
Schafflick, D., Wolbert, J., Heming, M., Thomas, C., Hartlehnert, M., Börsch, A., Ricci, A., Martín-Salamanca, S., Li, X., Lu, I., et al. (2021) · Nature Neuroscience · doi:10.1038/s41593-021-00880-y · Cited by 181 · see citing works
Louveau, A., Mesquita, S. D., & Kipnis, J. (2016) · Neuron · doi:10.1016/j.neuron.2016.08.027 · Cited by 175 · see citing works
The Choroid Plexus in Healthy and Diseased Brain
Kaur, C., Rathnasamy, G., & Ling, E.-A. (2016) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/nlv030 · Cited by 176 · see citing works
Mathur, V., Burai, R., Vest, R. T., Bonanno, L. N., Lehallier, B., Zardeneta, M. E., Mistry, K. N., Do, D., Marsh, S. E., Abud, E. M., et al. (2017) · Neuron · doi:10.1016/j.neuron.2017.11.032 · Cited by 175 · see citing works
Dá Mesquita, S., Ferreira, A. C., Sousa, J. C., Correia-Neves, M., Sousa, N., & Marques, F. (2016) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.06.014 · Cited by 166 · see citing works
Evidence supporting an altered immune response in ASD
Mead, J., & Ashwood, P. (2015) · Immunology Letters · doi:10.1016/j.imlet.2014.11.006 · Cited by 165 · see citing works
CNS Repair Requires Both Effector and Regulatory T Cells with Distinct Temporal and Spatial Profiles
Rapôso, C., Graubardt, N., Cohen, M., Eitan, C., London, A., Berkutzki, T., & Schwartz, M. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.0076-14.2014 · Cited by 161 · see citing works
Self-citationKann, O., Almouhanna, F., & Chausse, B. (2022) · Trends in Neurosciences · doi:10.1016/j.tins.2022.10.007 · Cited by 150 · see citing works
Klotho controls the brain-immune system interface in the choroid plexus
Zhu, L., Stein, L. R., Kim, D., Ho, K., Yu, G.-Q., Zhan, L., Larsson, T. E., & Mucke, L. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1808609115 · Cited by 148 · see citing works
Human T Cell Leukemia Virus Type 1: Persistence and Pathogenesis
Bangham, C. R. M. (2017) · Annual Review of Immunology · doi:10.1146/annurev-immunol-042617-053222 · Cited by 147 · see citing works
The choroid plexus: a missing link in our understanding of brain development and function
Saunders, N. R., Dzięgielewska, K. M., Fame, R. M., Lehtinen, M. K., & Liddelow, S. A. (2022) · Physiological Reviews · doi:10.1152/physrev.00060.2021 · Cited by 141 · see citing works
Type I/II Interferon Balance in the Regulation of Brain Physiology and Pathology
Deczkowska, A., Baruch, K., & Schwartz, M. (2016) · Trends in Immunology · doi:10.1016/j.it.2016.01.006 · Cited by 125 · see citing works
Self-citationAlzheimer’s Retinopathy: Seeing Disease in the Eyes
Mirzaei, N., Shi, H., Oviatt, M., Doustar, J., Rentsendorj, A., Fuchs, D.-T. S., Sheyn, J., Black, K. L., Koronyo, Y., & Koronyo‐Hamaoui, M. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.00921 · Cited by 130 · see citing works
Th17 and Cognitive Impairment: Possible Mechanisms of Action
Cipollini, V., Anrather, J., Orzi, F., & Iadecola, C. (2019) · Frontiers in Neuroanatomy · doi:10.3389/fnana.2019.00095 · Cited by 131 · see citing works
Insulin, Aging, and the Brain: Mechanisms and Implications
Akintola, A. A., & van Heemst, D. (2015) · Frontiers in Endocrinology · doi:10.3389/fendo.2015.00013 · Cited by 123 · see citing works
The gut-brain vascular axis in neuroinflammation
Carloni, S., & Rescigno, M. (2023) · Seminars in Immunology · doi:10.1016/j.smim.2023.101802 · Cited by 123 · see citing works
Neuroinflammation in Mood Disorders: Role of Regulatory Immune Cells
Bauer, M. E., & Teixeira, A. L. (2021) · NeuroImmunoModulation · doi:10.1159/000515594 · Cited by 125 · see citing works
Zheng, J., Chen, T., Wang, K., Peng, C., Zhao, M., Xie, Q., Li, B., Lin, H., Zhao, Z., Ji, Z., et al. (2024) · ACS Nano · doi:10.1021/acsnano.3c10541 · Cited by 122 · see citing works
Stopa, E. G., Tanis, K. Q., Miller, M. C., Nikonova, E. V., Podtelezhnikov, A. A., Finney, E. M., Stone, D. J., Camargo, L. M., Parker, L., Verma, A. M., et al. (2018) · Fluids and Barriers of the CNS · doi:10.1186/s12987-018-0102-9 · Cited by 118 · see citing works
IFN‐γ promotes transendothelial migration of CD4+ T cells across the blood–brain barrier
Sonar, S. A., Shaikh, S., Joshi, N., Atre, A. N., & Lal, G. (2017) · Immunology and Cell Biology · doi:10.1038/icb.2017.56 · Cited by 114 · see citing works
The Choroid Plexus Functions as a Niche for T-Cell Stimulation Within the Central Nervous System
Strominger, I., Elyahu, Y., Berner, O., Reckhow, J. D., Mittal, K., Nemirovsky, A., & Monsonego, A. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01066 · Cited by 111 · see citing works
Nishihara, H., Soldati, S. G., Mossu, A., Rosito, M., Rudolph, H., Müller, W. A., Latorre, D., Sallusto, F., Sospedra, M., Martinꝉ, R., et al. (2020) · Fluids and Barriers of the CNS · doi:10.1186/s12987-019-0165-2 · Cited by 114 · see citing works
Immunotherapy in CNS cancers: the role of immune cell trafficking
Ratnam, N. M., Gilbert, M. R., & Giles, A. J. (2018) · Neuro-Oncology · doi:10.1093/neuonc/noy084 · Cited by 110 · see citing works
Macrophages on the margin: choroid plexus immune responses
Cui, J., Xu, H., & Lehtinen, M. K. (2021) · Trends in Neurosciences · doi:10.1016/j.tins.2021.07.002 · Cited by 110 · see citing works
Glial scar and immune cell involvement in tissue remodeling and repair following acute CNS injuries
Rapôso, C., & Schwartz, M. (2014) · Glia · doi:10.1002/glia.22676 · Cited by 107 · see citing works
Self-citationMietelska‐Porowska, A., & Wojda, U. (2017) · Journal of Immunology Research · doi:10.1155/2017/4626540 · Cited by 107 · see citing works
Kunis, G., Baruch, K., Miller, O., & Schwartz, M. (2015) · The Journal of Neuroscience · doi:10.1523/jneurosci.3644-14.2015 · Cited by 105 · see citing works
Self-citationAn Act of Balance Between Adaptive and Maladaptive Immunity in Depression: a Role for T Lymphocytes
Toben, C. G., & Baune, B. T. (2015) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-015-9620-2 · Cited by 98 · see citing works
Chaban, V., Clarke, G. J. B., Skandsen, T., Islam, R., Einarsen, C. E., Vik, A., Damås, J. K., Mollnes, T. E., Haberg, A. K., & Pischke, S. E. (2020) · Journal of Neurotrauma · doi:10.1089/neu.2019.6963 · Cited by 96 · see citing works
Choroid plexus-cerebrospinal fluid route for monocyte-derived macrophages after stroke
Ge, R., Tornero, D., Hirota, M., Monni, E., Laterza, C., Lindvall, O., & Kokaia, Z. (2017) · Journal of Neuroinflammation · doi:10.1186/s12974-017-0909-3 · Cited by 95 · see citing works
Emerging Role of PD-1 in the Central Nervous System and Brain Diseases
Zhao, J., Roberts, A., Wang, Z., Savage, J. T., & Ji, R. (2021) · Neuroscience Bulletin · doi:10.1007/s12264-021-00683-y · Cited by 93 · see citing works
Stock, A. D., Gelb, S., Pasternak, O., Ben‐Zvi, A., & Putterman, C. (2017) · Autoimmunity Reviews · doi:10.1016/j.autrev.2017.04.008 · Cited by 93 · see citing works
Liston, A., Pasciuto, E., Fitzgerald, D. C., & Yshii, L. (2023) · Nature reviews. Immunology · doi:10.1038/s41577-023-00960-z · Cited by 92 · see citing works
Mesquita, S. D., Ferreira, A. C., Gao, F., Coppola, G., Geschwind, D. H., Sousa, J. C., Correia‐Neves, M., Sousa, N., Palha, J. A., & Marques, F. (2015) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2015.06.008 · Cited by 86 · see citing works
Bsibsi, M., Peferoen, L., Holtman, I., Nacken, P., Gerritsen, W., Witte, M., van Horssen, J., Eggen, B., van der Valk, P., Amor, S., et al. (2014) · Acta Neuropathologica · doi:10.1007/s00401-014-1317-8 · Cited by 87 · see citing works
Protective Autoimmunity: A Unifying Model for the Immune Network Involved in CNS Repair
Schwartz, M., & Raposo, C. (2014) · The Neuroscientist · doi:10.1177/1073858413516799 · Cited by 86 · see citing works
Self-citationStrazielle, N., Creidy, R., Malcus, C., Boucraut, J., & Ghersi‐Egea, J. (2016) · PLoS ONE · doi:10.1371/journal.pone.0150945 · Cited by 83 · see citing works
Schwartz, M., & Baruch, K. (2014) · Journal of Autoimmunity · doi:10.1016/j.jaut.2014.08.002 · Cited by 82 · see citing works
Self-citationUnique aspects of IFN ‐γ/ STAT1 signaling in neurons
Clark, D. N., Begg, L. R., & Filiano, A. J. (2022) · Immunological Reviews · doi:10.1111/imr.13092 · Cited by 81 · see citing works
The role of neutrophils in the dysfunction of central nervous system barriers
Santos-Lima, B., Pietronigro, E. C., Terrabuio, E., Zenaro, E., & Constantin, G. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.965169 · Cited by 82 · see citing works
Zuo, Z., Qi, F., Yang, J., Wang, X., Wu, Y., Wen, Y., Yuan, Q., Zou, J., Guo, K., & Yao, Z. B. (2017) · Neurobiology of Disease · doi:10.1016/j.nbd.2017.02.001 · Cited by 78 · see citing works
Ren, H., Chen, X., Tian, M., Zhou, J., Ouyang, H., & Zhang, Z. (2018) · Advanced Science · doi:10.1002/advs.201800529 · Cited by 75 · see citing works
Protective and Regenerative Roles of T Cells in Central Nervous System Disorders
Evans, F., Dittmer, M., de la Fuente, A. G., & Fitzgerald, D. C. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.02171 · Cited by 76 · see citing works
Baruch, K., Kertser, A., Porat, Z., & Schwartz, M. (2015) · The EMBO Journal · doi:10.15252/embj.201591468 · Cited by 75 · see citing works
Self-citationLiu, C., Wang, R., Yi, Y., Gao, Z., & Chen, Y. (2017) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2017.10.014 · Cited by 77 · see citing works
Rahimian, R., Belliveau, C., Chen, R., & Mechawar, N. (2022) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2022.871997 · Cited by 73 · see citing works
Brain interference: Revisiting the role of IFNγ in the central nervous system
Monteiro, S., Roque, S., Marques, F., Correia‐Neves, M., & Cerqueira, J. (2017) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2017.05.003 · Cited by 71 · see citing works
Gelb, S., Stock, A. D., Anzi, S., Putterman, C., & Ben‐Zvi, A. (2018) · Journal of Autoimmunity · doi:10.1016/j.jaut.2018.03.001 · Cited by 72 · see citing works
Kwon, M., Noh, M., Oh, K., Cho, K., Kang, B., Kim, K., Kim, Y., & Kim, S. H. (2014) · Journal of Neurochemistry · doi:10.1111/jnc.12814 · Cited by 70 · see citing works
Lazarevic, I., Soldati, S. G., Mapunda, J. A., Rudolph, H., Rosito, M., de Oliveira, A. C., Enzmann, G. U., Nishihara, H., Ishikawa, H., Tenenbaum, T., et al. (2023) · Fluids and Barriers of the CNS · doi:10.1186/s12987-023-00441-4 · Cited by 69 · see citing works
Tertiary lymphoid structures in the choroid plexus in neuropsychiatric lupus
Stock, A. D., Der, E. B., Gelb, S., Huang, M. W., Weidenheim, K. M., Ben‐Zvi, A., & Putterman, C. (2019) · JCI Insight · doi:10.1172/jci.insight.124203 · Cited by 65 · see citing works
Choroid Plexus in Alzheimer’s Disease—The Current State of Knowledge
Gião, T., Teixeira, T., Almeida, M. R., & Cardoso, I. (2022) · Biomedicines · doi:10.3390/biomedicines10020224 · Cited by 64 · see citing works
Engineered T cell therapy for central nervous system injury
Gao, W., Kim, M. W., Dykstra, T., Du, S., Boskovic, P., Lichti, C. F., Ruiz-Cardozo, M. A., Gu, X., Shapira, T. W., Rustenhoven, J., et al. (2024) · Nature · doi:10.1038/s41586-024-07906-y · Cited by 64 · see citing works
The subfornical organ is a nucleus for gut-derived T cells that regulate behaviour
Yoshida, T. M., Nguyen, M. T., Zhang, L., Lu, B. Y., Zhu, B., Murray, K. N., Mineur, Y. S., Zhang, C., Xu, D., Lin, E., et al. (2025) · Nature · doi:10.1038/s41586-025-09050-7 · Cited by 67 · see citing works
The choroid plexus as a sex hormone target: Functional implications
Santos, C. R. A., Duarte, A. C., Quintela, T., Tomás, J., Albuquerque, T., Marques, F., Palha, J. A., & Gonçalves, I. (2016) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2016.12.002 · Cited by 66 · see citing works
Systemic inflammation, neuroinflammation and perioperative neurocognitive disorders
Jia, S., Yang, H., Huang, F., & Fan, W. (2023) · Inflammation Research · doi:10.1007/s00011-023-01792-2 · Cited by 63 · see citing works
Long-term, West Nile virus-induced neurological changes: A comparison of patients and rodent models
Fulton, C. M., Beasley, D. W. C., Bente, D. A., & Dineley, K. T. (2020) · Brain Behavior & Immunity - Health · doi:10.1016/j.bbih.2020.100105 · Cited by 58 · see citing works
Impact of aging immune system on neurodegeneration and potential immunotherapies
Liang, Z., Zhao, Y., Ruan, L., Zhu, L., Jin, K., Zhuge, Q., Su, D., & Zhao, Y. L. (2017) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2017.07.006 · Cited by 61 · see citing works
Roselli, F., Chandrasekar, A., & Morganti-Kossmann, M. C. (2018) · Frontiers in Neurology · doi:10.3389/fneur.2018.00458 · Cited by 60 · see citing works
Neural Stem Cells for Early Ischemic Stroke
Hamblin, M. H., & Lee, J. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22147703 · Cited by 59 · see citing works
Macrophage compartmentalization in the brain and cerebrospinal fluid system
Munro, D. A. D., Movahedi, K., & Priller, J. (2022) · Science Immunology · doi:10.1126/sciimmunol.abk0391 · Cited by 55 · see citing works
- Authors
- Kunis, G., Baruch, K., Rosenzweig, N., Kertser, A., Miller, O., Berkutzki, T., & Schwartz, M.
- Affiliations
- Weizmann Institute of Science (IL)
- Venue
- Brain
- Publisher
- Oxford University Press (OUP)
- Published
- 2013-10-01
- Volume
- 136
- Issue
- 11
- Pages
- 3427-3440
- ISSN
- 0006-8950 (ISSN-L)
- 1460-2156
- OpenAlex
- W2112350141
- Cited by
- 321
- References
- 57
- Citations by year
- 2026: 14 · 2025: 28 · 2024: 27 · 2023: 31 · 2022: 34 · 2021: 26 · 2020: 28 · 2019: 23 · 2018: 18 · 2017: 25 · 2016: 22 · 2015: 25 · 2014: 17 · 2013: 3
- FWCI
- 12.53
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Cerebrospinal fluid and hydrocephalus
- Keywords
- choroid plexus, interferon-gamma, choroid plexus epithelium, Th1 cells, regulatory T cells, Th2 cells, interferon-gamma receptor, TNF-α, cerebrospinal fluid, spinal cord injury, CNS repair, immune surveillance, monocyte-derived macrophages, CD4+ T cells, bone marrow chimeric mice
- MeSH terms
- Interferon gamma Receptor, Animals, Cell Movement, Central Nervous System, Choroid Plexus, Epithelium, Female, Interferon-gamma, Male, Mice, Inbred C57BL, Receptors, Interferon, Mice, Knockout, Protein Transport, 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
