Capture, crawl, cross: the T cell code to breach the blood–brain barriers
Open accessAbstract
The central nervous system (CNS) is an immunologically privileged site to which access of circulating immune cells is tightly controlled by the endothelial blood-brain barrier (BBB; see Glossary) localized in CNS microvessels, and the epithelial blood-cerebrospinal fluid barrier (BCSFB) within the choroid plexus. As a result of the specialized structure of the CNS barriers, immune cell entry into the CNS parenchyma involves two differently regulated steps: migration of immune cells across the BBB or BCSFB into the cerebrospinal fluid (CSF)-drained spaces of the CNS, followed by progression across the glia limitans into the CNS parenchyma. With a focus on multiple sclerosis (MS) and its animal models, this review summarizes the distinct molecular mechanisms required for immune cell migration across the different CNS barriers.
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 experimental autoimmune encephalomyelitis models, a key pathophysiological event is encephalitogenic leukocyte CNS infiltration across the blood-brain barrier via sequential steps of capture, rolling, activation, adhesion, crawling, and diapedesis in postcapillary venules, capillaries, and mid-capillaries.
“Experimental findings in MS models of chronic and relapsing EAE have shown that a key pathophysiological event is encephalitogenic leukocyte CNSinfiltration across the BBB that occurs via sequential steps of capture, rolling, activation, adhesion, crawling, and diapedesis in postcapillary venules, capillaries, and mid-capillaries (161, 182, 215, 216, 456, 617)”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [161]
Paracellular diapedesis is regulated by endothelial VE-cadherin, JAM-A, ESAM, PECAM1, and CD99 and leukocyte LFA-1, PECAM1, and CD99.
“Paracellular diapedesis is regulated by endothelial VE-cadherin, JAM-A, ESAM, PECAM1, and CD99 and leukocyte LFA-1, PECAM1, and CD99 (161, 215, 617) (FIGURE 10) .”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [161]
Leukocyte migration across the BBB is limited to very few activated CD8+ and CD4+ T cells but not innate immune cells.
“In fact, leukocyte migration across the BBB is limited to very few activated CD8+ and CD4+ T cells but not innate immune cells (80).”
From The anatomy and immunology of vasculature in the central nervous system (2019) · cites this paper as [80]
Cites
Prevention of experimental autoimmune encephalomyelitis by antibodies against α4βl integrin
Yednock, T. A., Cannon, C., Fritz, L. C., Sánchez‐Madrid, F., Steinman, L., & Karin, N. (1992) · Nature · doi:10.1038/356063a0 · Cited by 1,737 · 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
Self-citationInflammatory cortical demyelination in early multiple sclerosis.
Lucchinetti, C. F., Popescu, B. F. G., Bunyan, R. F., Moll, N. M., Roemer, S. F., Lassmann, H., Brück, W., Parisi, J. E., Scheithauer, B. W., Giannini, C., et al. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1100648 · Cited by 1,103 · see citing works
Self-citationDendritic cells permit immune invasion of the CNS in an animal model of multiple sclerosis
Greter, M., Heppner, F. L., Lemos, M. P., Odermatt, B. M., Goebels, N., Laufer, T., Noelle, R. J., & Becher, B. (2005) · Nature Medicine · doi:10.1038/nm1197 · Cited by 862 · see citing works
The Hedgehog Pathway Promotes Blood-Brain Barrier Integrity and CNS Immune Quiescence
Alvarez, J. I., Dodelet-Devillers, A., Kebir, H., Ifergan, I., Fabre, P. J., Terouz, S., Sabbagh, M., Wosik, K., Bourbonnière, L., Bernard, M., et al. (2011) · Science · doi:10.1126/science.1206936 · Cited by 845 · see citing works
Wnt/β-catenin signaling controls development of the blood–brain barrier
Liebner, S., Corada, M., Bangsow, T., Babbage, J., Taddei, A., Czupalla, C. J., Reis, M., Felici, A., Wolburg, H., Fruttiger, M., et al. (2008) · The Journal of Cell Biology · doi:10.1083/jcb.200806024 · Cited by 793 · see citing works
The blood–brain and the blood–cerebrospinal fluid barriers: function and dysfunction
Engelhardt, B., & Sorokin, L. M. (2009) · Seminars in Immunopathology · doi:10.1007/s00281-009-0177-0 · Cited by 792 · see citing works
Self-citationInflammation Dampened by Gelatinase A Cleavage of Monocyte Chemoattractant Protein-3
McQuibban, G. A., Gong, J.-H., Tam, E. M., McCulloch, C. A., Clark‐Lewis, I., & Overall, C. M. (2000) · Science · doi:10.1126/science.289.5482.1202 · Cited by 772 · see citing works
Cellular immune reactivity within the CNS
Wekerle, H., Linington, C., Lassmann, H., & Meyermann, R. (1986) · Trends in Neurosciences · doi:10.1016/0166-2236(86)90077-9 · Cited by 767 · see citing works
The adhesion molecule and cytokine profile of multiple sclerosis lesions
Cannella, B., & Raine, C. S. (1995) · Annals of Neurology · doi:10.1002/ana.410370404 · Cited by 759 · see citing works
Effector T cell interactions with meningeal vascular structures in nascent autoimmune CNS lesions.
Bartholomäus, I., Kawakami, N., Odoardi, F., Schläger, C., Miljkovic, D., Ellwart, J. W., Klinkert, W. E. F., Flügel-Koch, C., Issekutz, T. B., Wekerle, H., et al. (2009) · Nature · doi:10.1038/nature08478 · Cited by 685 · see citing works
Carare, R. O., Bernardes‐Silva, M., Newman, T. A., Page, A. M., Nicoll, J. A. R., Perry, V. H., & Weller, R. O. (2008) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.2007.00926.x · Cited by 665 · see citing works
Mechanisms of Leukocyte Transendothelial Migration
Müller, W. A. (2011) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathol-011110-130224 · Cited by 627 · see citing works
Breaching multiple barriers: leukocyte motility through venular walls and the interstitium
Nourshargh, S., Hordijk, P. L., & Sixt, M. (2010) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2889 · Cited by 561 · see citing works
Agrawal, S., Anderson, P., Durbeej, M., van Rooijen, N., Ivars, F., Opdenakker, G., & Sorokin, L. M. (2006) · The Journal of Experimental Medicine · doi:10.1084/jem.20051342 · Cited by 559 · 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
Self-citationSixt, M., Engelhardt, B., Pausch, F., Hallmann, R., Wendler, O., & Sorokin, L. M. (2001) · The Journal of Cell Biology · doi:10.1083/jcb.153.5.933 · Cited by 509 · see citing works
Self-citationSobel, R. A., Mitchell, M. E., & Fondren, G. (1990) · PubMed · Cited by 390 · see citing works
Fuentes, M. E., Durham, S. K., Swerdel, M. R., Lewin, A. C., Barton, D. S., Megill, J. R., Bravo, R., & Lira, S. A. (1995) · The Journal of Immunology · doi:10.4049/jimmunol.155.12.5769 · Cited by 384 · see citing works
Choroid plexus: biology and pathology
Wolburg, H., & Paulus, W. (2009) · Acta Neuropathologica · doi:10.1007/s00401-009-0627-8 · Cited by 376 · see citing works
Tran, E., Hoekstra, K., van Rooijen, N., Dijkstra, C., & Owens, T. (1998) · Journal of Immunology · doi:10.4049/jimmunol.161.7.3767 · Cited by 373 · see citing works
Hickey, W. F. (1991) · Brain Pathology · doi:10.1111/j.1750-3639.1991.tb00646.x · Cited by 357 · see citing works
Vajkoczy, P., Laschinger, M., & Engelhardt, B. (2001) · Journal of Clinical Investigation · doi:10.1172/jci12440 · Cited by 357 · see citing works
Self-citationPerivascular Spaces and the Two Steps to Neuroinflammation
Owens, T., Bechmann, I., & Engelhardt, B. (2008) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e31818f9ca8 · Cited by 352 · see citing works
Self-citationEngelhardt, B., & Wolburg, H. (2004) · European Journal of Immunology · doi:10.1002/eji.200425327 · Cited by 334 · see citing works
Self-citationThe Vascular System of the Cerebral Cortex
Bär, T. (1980) · Advances in anatomy, embryology and cell biology · doi:10.1007/978-3-642-67432-7 · Cited by 305 · see citing works
Steiner, O., Coisne, C., Cecchelli, R., Boscacci, R., Deutsch, U., Engelhardt, B., & Lyck, R. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.0903732 · Cited by 293 · see citing works
Self-citationLossinsky, A. S., & Shivers, R. R. (2004) · PubMed · doi:10.14670/hh-19.535 · Cited by 275 · see citing works
CCR7 signalling as an essential regulator of CNS infiltration in T-cell leukaemia
Buonamici, S., Trimarchi, T., Ruocco, M. G., Reavie, L. B., Cathelin, S., Mar, B. G., Klinakis, A., Lukyanov, Y., Tseng, J., Şen, F., et al. (2009) · Nature · doi:10.1038/nature08020 · Cited by 266 · see citing works
Wu, C., Ivars, F., Anderson, P. O., Hallmann, R., Vestweber, D., Nilsson, P., Robenek, H., Tryggvason, K., Song, J., Korpos, É., et al. (2009) · Nature Medicine · doi:10.1038/nm.1957 · Cited by 264 · see citing works
Engelhardt, B., & Coisne, C. (2011) · Fluids and Barriers of the CNS · doi:10.1186/2045-8118-8-4 · Cited by 248 · see citing works
Self-citationMcCandless, E. E., Wang, Q., Woerner, B. M., Harper, J. M., & Klein, R. S. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.11.8053 · Cited by 247 · 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
Self-citationPiccio, L., Rossi, B., Scarpini, E., Laudanna, C., Giagulli, C., Issekutz, A. C., Vestweber, D., Butcher, E. C., & Constantin, G. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.168.4.1940 · Cited by 245 · see citing works
Rothhammer, V., Heink, S., Petermann, F., Srivastava, R., Claussen, M. C., Hemmer, B., & Korn, T. (2011) · The Journal of Experimental Medicine · doi:10.1084/jem.20110434 · Cited by 242 · see citing works
Cross, A. H., Cannella, B., Cf, B., et al. (1990) · PubMed · Cited by 233 · see citing works
Cruz-Orengo, L., Holman, D. W., Dorsey, D., Zhou, L., Zhang, P., Wright, M., McCandless, E. E., Patel, J. R., Luker, G. D., Littman, D. R., et al. (2011) · Journal of Experimental Medicine · doi:10.1084/jem.20102010 · Cited by 231 · see citing works
Differential adhesion molecule requirements for immune surveillance and inflammatory recruitment
Carrithers, M. D., Visintin, I., Kang, S. J., & Janeway, C. A. (2000) · Brain · doi:10.1093/brain/123.6.1092 · Cited by 220 · see citing works
Steffen, B. J., Butcher, E. C., & Engelhardt, B. (1994) · PubMed Central · Cited by 215 · see citing works
Self-citationWeller, R. O., Engelhardt, B., & Phillips, M. J. (1996) · Brain Pathology · doi:10.1111/j.1750-3639.1996.tb00855.x · Cited by 213 · see citing works
Self-citationAnandasabapathy, 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 206 · see citing works
McCandless, E. E., Piccio, L., Woerner, B. M., Schmidt, R. E., Rubin, J. B., Cross, A. H., & Klein, R. S. (2008) · The American Journal of Pathology · doi:10.2353/ajpath.2008.070918 · Cited by 206 · see citing works
Engelhardt, B., Laschinger, M., Schulz, M., Samulowitz, U., Vestweber, D., & Hoch, G. (1998) · Journal of Clinical Investigation · doi:10.1172/jci4271 · Cited by 203 · see citing works
Self-citationMechanisms for transcellular diapedesis: probing and pathfinding by `invadosome-like protrusions'
Carman, C. V. (2009) · Journal of Cell Science · doi:10.1242/jcs.047522 · Cited by 198 · see citing works
Tight Junctions in Brain Barriers During Central Nervous System Inflammation
Coisne, C., & Engelhardt, B. (2011) · Antioxidants and Redox Signaling · doi:10.1089/ars.2011.3929 · Cited by 186 · see citing works
Self-citation(1995) · PubMed Central · Cited by 182 · see citing works
Archelos, J. J., Jung, S., Mäurer, M., Schmied, M. C., Lassmann, H., Tamatani, T., Miyasaka, M., Toyka, K. V., & Hartung, H. (1993) · Annals of Neurology · doi:10.1002/ana.410340209 · Cited by 180 · see citing works
Interferon-β directly influences monocyte infiltration into the central nervous system
Floris, S., Ruuls, S. R., Wierinckx, A., et al. (2002) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(02)00098-x · Cited by 180 · see citing works
Shulman, 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
Bär, T. (1980) · Advances in anatomy, embryology and cell biology · doi:10.1007/978-3-642-67432-7_1 · Cited by 167 · see citing works
All vertebrates started out with a glial blood‐brain barrier 4–500 million years ago
Bundgaard, M., & Abbott, N. J. (2008) · Glia · doi:10.1002/glia.20642 · Cited by 163 · see citing works
Pfeiffer, F., Schäfer, J., Lyck, R., Makrides, V., Brunner, S., Schaeren-Wiemers, N., Deutsch, U., & Engelhardt, B. (2011) · Acta Neuropathologica · doi:10.1007/s00401-011-0883-2 · Cited by 160 · see citing works
Self-citationActual problems of the cerebrospinal fluid-contacting neurons
Béla, V. I. G. H., & Vigh‐Teichmann, I. (1998) · Microscopy Research and Technique · doi:10.1002/(sici)1097-0029(19980401)41:1 · Cited by 151 · see citing works
Laschinger, M., & Engelhardt, B. (2000) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(99)00156-3 · Cited by 149 · see citing works
Self-citationOn the mode of entry of blood vessels into the cerebral cortex.
Jones, E. G. (1970) · PubMed · Cited by 146 · see citing works
Bö, L., Peterson, J. W., Mørk, S. J., Hoffman, P. A., Gallatin, M. W., Ransohoff, R. M., & Trapp, B. D. (1996) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-199655100-00006 · Cited by 144 · see citing works
Self-citationKivisäkk, 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
Self-citationKrumbholz, M., Theil, D. J., Steinmeyer, F., Cepok, S., Hemmer, B., Hofbauer, M., Farina, C., Derfuss, T. J., Junker, A., Arzberger, T., et al. (2007) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2007.07.024 · Cited by 136 · see citing works
Bullard, D. C., Hu, X., Schoeb, T. R., et al. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.2.851 · Cited by 135 · see citing works
Ifergan, I., Kébir, H., Alvarez, J. I., Marceau, G., Bernard, M., Bourbonnière, L., Poirier, J., Duquette, P., Talbot, P. J., Arbour, N., et al. (2011) · Brain · doi:10.1093/brain/awr268 · Cited by 129 · see citing works
Is the pial microvessel a good model for blood-brain barrier studies?
Allt, G., & Lawrenson, J. G. (1997) · Brain Research Reviews · doi:10.1016/s0165-0173(97)00011-8 · Cited by 118 · see citing works
Coisne, C., Mao, W., & Engelhardt, B. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0803418 · Cited by 114 · see citing works
Self-citationBrain endothelium lack one of two pathways of P-selectin-mediated neutrophil adhesion
Barkalow, F., Goodman, M., Gerritsen, M., & Mayadas, T. (1996) · Blood · doi:10.1182/blood.v88.12.4585.bloodjournal88124585 · Cited by 110 · see citing works
Bauer, M., Brakebusch, C., Coisne, C., Sixt, M., Wekerle, H., Engelhardt, B., & Fässler, R. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0808909106 · Cited by 107 · see citing works
Self-citationAnti-adhesion molecule therapy in experimental autoimmune encephalomyelitis
Cannella, B., Cross, A. H., & Raine, C. S. (1993) · Journal of Neuroimmunology · doi:10.1016/0165-5728(93)90232-n · Cited by 104 · see citing works
Steiner, O., Coisne, C., Engelhardt, B., & Lyck, R. (2011) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2010.96 · Cited by 94 · see citing works
Self-citationProgressive multifocal leukoencephalopathy
Weissert, R. (2010) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2010.09.021 · Cited by 93 · see citing works
Kerfoot, S. M., Norman, M. U., Lapointe, B. M., Bonder, C. S., Zbytnuik, L. D., & Kubes, P. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.176.10.6225 · Cited by 88 · see citing works
VCAM‐1‐Positive Microglia Target Oligodendrocytes at the Border of Multiple Sclerosis Lesions
Peterson, J. W., Bö, L., Mörk, S., Chang, A., Ransohoff, R., & Trapp, B. (2002) · Journal of Neuropathology and Experimental Neurology · doi:10.1093/jnen/61.6.539 · Cited by 88 · see citing works
Self-citationUltrastructural 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
Self-citationRegulation and Functional Effects of Monocyte Migration across Human Brain-Derived Endothelial Cells
Seguin, R. M., Biernacki, K., Rotondo, R. L., Prat, A., & Antel, J. P. (2003) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/62.4.412 · Cited by 86 · see citing works
Jain, P., Coisne, C., Enzmann, G. U., Rottapel, R. K., & Engelhardt, B. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.0901404 · Cited by 85 · see citing works
Self-citationLaschinger, M., Vajkoczy, P., & Engelhardt, B. (2002) · European Journal of Immunology · doi:10.1002/1521-4141(200212)32:12 · Cited by 82 · see citing works
Self-citationCutting Edge: Loss of α4 Integrin Expression Differentially Affects the Homing of Th1 and Th17 Cells
Glatigny, S., Duhen, R., Oukka, M., & Bettelli, E. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1102515 · Cited by 82 · see citing works
Toft‐Hansen, H., Buist, R. J., Sun, X.-J., Schellenberg, A. E., Peeling, J., & Owens, T. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.10.7242 · Cited by 81 · see citing works
Imaging Correlates of Leukocyte Accumulation and CXCR4/CXCL12 in Multiple Sclerosis
Moll, N. M., Cossoy, M. B., Fisher, E., Staugaitis, S. M., Tucky, B. H., Rietsch, A. M., Chang, A., Fox, R. J., Trapp, B. D., & Ransohoff, R. M. (2009) · Archives of Neurology · doi:10.1001/archneurol.2008.512 · Cited by 75 · see citing works
Self-citationRequirements for passage of T lymphocytes across non-inflamed retinal microvessels
Xu, H., Manivannan, A., Liversidge, J., Sharp, P. F., Forrester, J. V., & Crane, I. J. (2003) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(03)00258-3 · Cited by 64 · see citing works
Bahbouhi, B., Berthelot, L., Pettré, S., Michel, L., Wiertlewski, S., Weksler, B. B., Romero, I. A., Miller, F., Couraud, P., Brouard, S., et al. (2009) · Journal of Leukocyte Biology · doi:10.1189/jlb.1008666 · Cited by 61 · see citing works
Man, S., Tucky, B. H., Bagheri, N., Li, X., Kochar, R., & Ransohoff, R. M. (2009) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2009.03.008 · Cited by 54 · see citing works
Self-citationProvencio, J. J., Kivisäkk, P., Tucky, B. H., Luciano, M. G., & Ransohoff, R. M. (2005) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2005.03.003 · Cited by 42 · see citing works
Self-citationYoung, K. G., MacLean, S., Dudani, R., Krishnan, L., & Sad, S. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1100695 · Cited by 33 · see citing works
Hu, X., Barnum, S. R., Wohler, J. E., et al. (2010) · Molecular Immunology · doi:10.1016/j.molimm.2010.03.005 · Cited by 28 · see citing works
Döring, A., Pfeiffer, F., Meier, M., Dehouck, B., Tauber, S., Deutsch, U., & Engelhardt, B. (2011) · European Journal of Immunology · doi:10.1002/eji.201040912 · Cited by 28 · see citing works
Self-citationScalabrini, D., Galimberti, D., Fenoglio, C., Comi, C., Riz, M. A. D., Venturelli, E., Castelli, L., Piccio, L. M., Ronzoni, M., Lovati, C., et al. (2005) · Neuroscience Letters · doi:10.1016/j.neulet.2005.06.059 · Cited by 13 · see citing works
Interactions of Selectins with PSGL-1 and Other Ligands
McEver, R. P. (2004) · Springer eBooks · doi:10.1007/978-3-662-05397-3_8 · Cited by 12 · see citing works
Editorial: PSGL-1—the hidden player in T cell trafficking into the brain in multiple sclerosis?
Engelhardt, B. (2009) · Journal of Leukocyte Biology · doi:10.1189/jlb.0509358 · Cited by 6 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Development, maintenance and disruption of the blood-brain barrier
Obermeier, B., Daneman, R., & Ransohoff, R. M. (2013) · Nature Medicine · doi:10.1038/nm.3407 · Cited by 2,452 · see citing works
Self-citationBlood-Brain Barrier: From Physiology to Disease and Back
Sweeney, M. D., Zhao, Z., Montagne, A., Nelson, A. R., & Zlokovic, B. V. (2019) · Physiological Reviews · doi:10.1152/physrev.00050.2017 · Cited by 2,294 · see citing works
The glymphatic system: a beginner's guide
Jessen, N. A., Munk, A. S. F., Lundgaard, I., & Nedergaard, M. (2015) · Neurochemical Research · doi:10.1007/s11064-015-1581-6 · Cited by 2,075 · see citing works
The movers and shapers in immune privilege of the CNS
Engelhardt, B., Vajkoczy, P., & Weller, R. O. (2017) · Nature Immunology · doi:10.1038/ni.3666 · Cited by 893 · see citing works
Self-citationRevisiting 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
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
Self-citationProgress in brain targeting drug delivery system by nasal route
Khan, A. R., Liu, M., Khan, M. W., & Zhai, G. (2017) · Journal of Controlled Release · doi:10.1016/j.jconrel.2017.09.001 · Cited by 402 · see citing works
Lim, S. Y., Lee, J. H., Gide, T. N., Menzies, A. M., Guminski, A., Carlino, M. S., Breen, E. J., Yang, J. Y. H., Ghazanfar, S., Kefford, R. F., et al. (2019) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-18-2795 · Cited by 381 · see citing works
Microglia Require CD4 T Cells to Complete the Fetal-to-Adult Transition
Pasciuto, E., Burton, O. T., Roca, C. P., Lagou, V., Rajan, W. D., Theys, T., Mancuso, R., Tito, R. Y., Kouser, L., Callaerts-Vegh, Z., et al. (2020) · Cell · doi:10.1016/j.cell.2020.06.026 · Cited by 368 · see citing works
Vascular, glial, and lymphatic immune gateways of the central nervous system
Engelhardt, B., Carare, R. O., Bechmann, I., Flügel, A., Laman, J. D., & Weller, R. O. (2016) · Acta Neuropathologica · doi:10.1007/s00401-016-1606-5 · Cited by 362 · see citing works
Self-citationTau and neuroinflammation: what impact for Alzheimer's disease and tauopathies?
Laurent, C., Buée, L., & Blum, D. (2018) · Biomedical Journal · doi:10.1016/j.bj.2018.01.003 · Cited by 348 · see citing works
The 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
Advances in Meningeal Immunity
Rua, R., & McGavern, D. B. (2018) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2018.04.003 · Cited by 326 · see citing works
Marchetti, L., & Engelhardt, B. (2020) · Vascular Biology · doi:10.1530/vb-19-0033 · Cited by 304 · see citing works
Harris, S. A., & Harris, E. A. (2015) · Journal of Alzheimer's Disease · doi:10.3233/jad-142853 · Cited by 279 · see citing works
Lopes Pinheiro, M. A., Kooij, G., Mizee, M. R., Kamermans, A., Enzmann, G., Lyck, R., Schwaninger, M., Engelhardt, B., & de Vries, H. E. (2016) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2015.10.018 · Cited by 247 · see citing works
Self-citationAstrocytic tight junctions control inflammatory CNS lesion pathogenesis
Horng, S., Therattil, A., Moyon, S., Gordon, A., Kim, K., Argaw, A. T., Hara, Y., Mariani, J. N., Sawai, S., Flodby, P., et al. (2017) · Journal of Clinical Investigation · doi:10.1172/jci91301 · Cited by 221 · see citing works
Vascular disruption and blood–brain barrier dysfunction in intracerebral hemorrhage
Keep, R. F., Zhou, N., Xiang, J., Andjelkovic, A. V., Hua, Y., & Xi, G. (2014) · Fluids and Barriers of the CNS · doi:10.1186/2045-8118-11-18 · Cited by 220 · see citing works
Deep cervical lymph node ligation aggravates AD‐like pathology of APP/PS1 mice
Wang, L., Zhang, Y., Zhao, Y., Marshall, C., Wu, T., & Xiao, M. (2019) · Brain Pathology · doi:10.1111/bpa.12656 · Cited by 199 · see citing works
How and why do T cells and their derived cytokines affect the injured and healthy brain?
Filiano, A. J., Gadani, S. P., & Kipnis, J. (2017) · Nature Reviews Neuroscience · doi:10.1038/nrn.2017.39 · Cited by 199 · see citing works
Tight junction dynamics: the role of junctional adhesion molecules (JAMs)
Garrido-Urbani, S., Bradfield, P. F., & Imhof, B. A. (2014) · Cell and Tissue Research · doi:10.1007/s00441-014-1820-1 · Cited by 154 · see citing works
Focusing on claudin-5: A promising candidate in the regulation of BBB to treat ischemic stroke
Lv, J., Hu, W., Yang, Z., Li, T., Jiang, S., Ma, Z., Chen, F., & Yang, Y. (2018) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2017.12.001 · Cited by 148 · see citing works
Mitophagy and cGAS–STING crosstalk in neuroinflammation
Zhou, X., Wang, J., Yu, L., Qiao, G., Qin, D., Yuen-Kwan Law, B., Ren, F., Wu, J., & Wu, A. (2024) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2024.05.012 · Cited by 131 · see citing works
Enzmann, G., Kargaran, S., & Engelhardt, B. (2018) · Therapeutic Advances in Neurological Disorders · doi:10.1177/1756286418794184 · Cited by 119 · see citing works
Self-citationRole of Macrophages in Brain Tumor Growth and Progression
Guadagno, E., Presta, I., Maisano, D., Donato, A., Pirrone, C., Cardillo, G., Corrado, S., Mignogna, C., Mancuso, T., Donato, G., et al. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19041005 · Cited by 118 · see citing works
Alquisiras-Burgos, I., Peralta-Arrieta, I., Alonso-Palomares, L. A., Zacapala-Gómez, A. E., Salmerón-Bárcenas, E. G., & Aguilera, P. (2021) · Molecular Neurobiology · doi:10.1007/s12035-020-02134-7 · Cited by 115 · see citing works
The role of the immune system in neurodegenerative disorders: Adaptive or maladaptive?
Doty, K. R., Guillot-Sestier, M.-V., & Town, T. (2015) · Brain Research · doi:10.1016/j.brainres.2014.09.008 · Cited by 104 · see citing works
Evidence that Meningeal mast cells can worsen stroke pathology in mice.
Arac, A., Grimbaldeston, M. A., Nepomuceno, A. R. B., Olayiwola, O., Pereira, M. P., Nishiyama, Y., Tsykin, A., Goodall, G. J., Schlecht, U., Vogel, H., et al. (2014) · The American Journal of Pathology · doi:10.1016/j.ajpath.2014.06.003 · Cited by 74 · see citing works
GFP-specific CD8 T cells enable targeted cell depletion and visualization of T-cell interactions
Agudo, J., Ruzo, A., Park, E. S., Sweeney, R., Kana, V., Wu, M., Zhao, Y., Egli, D., Merad, M., & Brown, B. D. (2015) · Nature Biotechnology · doi:10.1038/nbt.3386 · Cited by 64 · see citing works
Fischer, H. J., Schweingruber, N., Lühder, F., & Reichardt, H. M. (2013) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2013.04.001 · Cited by 34 · see citing works
Stromal cell niches in the inflamed central nervous system.
Pikor, N. B., Cupovic, J., Onder, L., Gommerman, J. L., & Ludewig, B. (2017) · The Journal of Immunology · doi:10.4049/jimmunol.1601566 · Cited by 33 · see citing works
The role of the adaptive immune system in the initiation and persistence of multiple sclerosis
Afzali, A. M., & Korn, T. (2025) · Seminars in Immunology · doi:10.1016/j.smim.2025.101947 · Cited by 25 · see citing works
- Authors
- Engelhardt, B., & Ransohoff, R. M.
- Affiliations
- University of Bern (CH)
- Cleveland Clinic (US)
- Corresponding author
- Engelhardt, Britta
- Venue
- Trends in Immunology
- Publisher
- Elsevier BV
- Published
- 2012-12
- Volume
- 33
- Issue
- 12
- Pages
- 579-589
- ISSN
- 1471-4906 (ISSN-L)
- OpenAlex
- W2045683532
- Cited by
- 686
- References
- 88
- Citations by year
- 2026: 43 · 2025: 49 · 2024: 50 · 2023: 45 · 2022: 56 · 2021: 49 · 2020: 56 · 2019: 42 · 2018: 59 · 2017: 45 · 2016: 52 · 2015: 55 · 2014: 42 · 2013: 42 · 2012: 1
- FWCI
- 4.17
- Type
- journal article
- Language
- en
- Open access
- green
- zenodo.org
- Licence
- Locations
- Trends in Immunology (publishedVersion)
- PubMed (publishedVersion)
- BORIS (University Library Bern) (submittedVersion)
- Zenodo (CERN European Organization for Nuclear Research) (submittedVersion, other-oa)
- Funders
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (K24 NS51400, P50NS38667, R21NS78420, R01NS32151, R01NS032151, K24NS051400, P50NS038667)
- Rocky Mountain Research Station
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Keywords
- blood-brain barrier, blood-CSF barrier, choroid plexus, T cell migration, glia limitans, multiple sclerosis, animal models of multiple sclerosis, cerebrospinal fluid
- MeSH terms
- Animals, Basement Membrane, Blood-Brain Barrier, Cell Movement, Central Nervous System, Humans, T-Lymphocytes
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