CNS lymphatic drainage and neuroinflammation are regulated by meningeal lymphatic vasculature.
Open accessAbstract
Neuroinflammatory diseases, such as multiple sclerosis, are characterized by invasion of the brain by autoreactive T cells. The mechanism for how T cells acquire their encephalitogenic phenotype and trigger disease remains, however, unclear. The existence of lymphatic vessels in the meninges indicates a relevant link between the CNS and peripheral immune system, perhaps affecting autoimmunity. Here we demonstrate that meningeal lymphatics fulfill two critical criteria: they assist in the drainage of cerebrospinal fluid components and enable immune cells to enter draining lymph nodes in a CCR7-dependent manner. Unlike other tissues, meningeal lymphatic endothelial cells do not undergo expansion during inflammation, and they express a unique transcriptional signature. Notably, the ablation of meningeal lymphatics diminishes pathology and reduces the inflammatory response of brain-reactive T cells during an animal model of multiple sclerosis. Our findings demonstrate that meningeal lymphatics govern inflammatory processes and immune surveillance of the CNS and pose a valuable target for therapeutic intervention.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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 5xFAD mice, meningeal leukocyte populations show significantly more B cells, CD4+ T cells, and CD8+ T cells at 11-12 months than at 5-6 months.
“Mass cytometric analysis of different meningeal leukocyte populations in 5xFAD mice at 5–6 and 11–12 months revealed a significant increase in the numbers of B cells, CD4+ T cells and CD8+ T cells in the older mice (Extended Data Fig. 2a–e) that can also be indicative of an accelerated impairment of meningeal lymphatic vasculature12.”
From Meningeal lymphatics affect microglia responses and anti-Aβ immunotherapy (2021) · cites this paper as [12]
Photoablation of meningeal lymphatics removes lymphatic vasculature lining the transverse sinus in the dorsal meninges.
“Meningeal lymphatic dysfunction was induced by a previously described method of photoablation5,12 that results in the loss of lymphatic vasculature lining the transverse sinus (in the dorsal meninges; Extended Data Fig. 3a, b).”
From Meningeal lymphatics affect microglia responses and anti-Aβ immunotherapy (2021) · cites this paper as [12]
In 13-14-month-old 5xFAD mice, dorsal meningeal lymphatic deterioration coincides with a significant rise in amyloid-beta deposition throughout the meninges, including along blood and lymphatic vessels.
“The deterioration of the lymphatic vasculature at the dorsal meninges observed in 13–14-month-old 5xFAD mice was accompanied by a significant increase in Aβ deposition throughout the meninges (Extended Data Fig. 1c–e), with extensive Aβ deposition along the blood and lymphatic vasculature (Extended Data Fig. 1a, insets) at anatomical locations previously shown as ‘hot spots’ along meningeal lymph”
From Meningeal lymphatics affect microglia responses and anti-Aβ immunotherapy (2021) · cites this paper as [12]
Initial lymphatics at the dorsal brain meninges are important for cerebrospinal fluid drainage.
“These results emphasize the importance of initial lymphatics at the dorsal brain meninges in CSF drainage5,12,18.”
From Meningeal lymphatics affect microglia responses and anti-Aβ immunotherapy (2021) · cites this paper as [12]
The dural lymphatics are a critical transport system of macromolecules, interstitial fluid, and CSF from the CNS into the cervical lymph nodes.
“The dural lymphatics are now recognized as a critical transport system of macromolecules, interstitial fluid, and CSF from the CNS into the cervical lymph nodes (Aspelund et al., 2015; Absinta et al., 2017; Louveau et al., 2018; Ahn et al., 2019).”
From Living on the Edge of the CNS: Meninges Cell Diversity in Health and Disease (2021) · cites this paper as Louveau et al., 2018
The medial prefrontal cortex is an integral structure for threat interpretations and regulates subcortical responses to threatening stimuli.
“An integral structure for threat interpretations is the medial prefrontal cortex (mPFC), which regulates subcortical responses to threatening stimuli14.”
From Meningeal γδ T cells regulate anxiety-like behavior via IL-17a signaling in neurons (2020) · cites this paper as [14]
Antigen drainage from the dura mater occurs by way of lymphatic vessels traversing the dura mater and draining to the deep cervical lymph nodes.
“Antigen drainage from the dura mater occurs in a similar fashion by way of lymphatic vessels traversing the dura mater and draining to the deep cervical lymph nodes (4, 5, 64).”
From The anatomy and immunology of vasculature in the central nervous system (2019) · cites this paper as [64]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Iliff, J. J., Wang, M., Liao, Y., Plogg, B. A., Peng, W., Gundersen, G. A., Benveniste, H., Vates, G. E., Deane, R., Goldman, S. A., et al. (2012) · Science Translational Medicine · doi:10.1126/scitranslmed.3003748 · Cited by 5,824 · 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
Self-citationImmunopathology of multiple sclerosis
Dendrou, C. A., Fugger, L., & Friese, M. A. (2015) · Nature Reviews Immunology · doi:10.1038/nri3871 · Cited by 2,215 · 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
Prox1 Function Is Required for the Development of the Murine Lymphatic System
Wigle, J. T., & Oliver, G. C. (1999) · Cell · doi:10.1016/s0092-8674(00)81511-1 · Cited by 1,581 · see citing works
Self-citationFunctional aspects of meningeal lymphatics in ageing and Alzheimer’s disease
Da Mesquita, S., Louveau, A., Vaccari, A., Smirnov, I., Cornelison, R. C., Kingsmore, K. M., Contarino, C., Onengut-Gumuscu, S., Farber, E., Raper, D., et al. (2018) · Nature · doi:10.1038/s41586-018-0368-8 · Cited by 1,445 · see citing works
Self-citationFunctionally specialized junctions between endothelial cells of lymphatic vessels
Baluk, P., Fuxe, J., Hashizume, H., Romano, T., Lashnits, E., Butz, S., Vestweber, D., Corada, M., Molendini, C., Dejana, E., et al. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20062596 · Cited by 1,006 · 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
A new look at cerebrospinal fluid circulation
Brinker, T., Stopa, E., Morrison, J., & Klinge, P. (2014) · Fluids and Barriers of the CNS · doi:10.1186/2045-8118-11-10 · Cited by 819 · see citing works
Regulation of learning and memory by meningeal immunity: a key role for IL-4
Derecki, N. C., Cardani, A. N., Yang, C. H., Quinnies, K. M., Crihfield, A., Lynch, K. R., & Kipnis, J. (2010) · Journal of Experimental Medicine · doi:10.1084/jem.20091419 · Cited by 800 · see citing works
Self-citationMa, Q., Ineichen, B. V., Detmar, M., & Proulx, S. T. (2017) · Nature Communications · doi:10.1038/s41467-017-01484-6 · Cited by 690 · see citing works
Absinta, M., Ha, S.-K., Nair, G., Sati, P., Luciano, N. J., Palisoc, M., Louveau, A., Zaghloul, K. A., Pittaluga, S., Kipnis, J., et al. (2017) · eLife · doi:10.7554/elife.29738 · Cited by 643 · see citing works
Understanding the functions and relationships of the glymphatic system and meningeal lymphatics
Louveau, A., Plog, B. A., Antila, S., Alitalo, K., Nedergaard, M., & Kipnis, J. (2017) · Journal of Clinical Investigation · doi:10.1172/jci90603 · Cited by 640 · see citing works
Self-citationLymphatic vascular defects promoted by Prox1 haploinsufficiency cause adult-onset obesity
Harvey, N. L., Srinivasan, R. S., Dillard, M. E., Johnson, N. C., Witte, M. H., Boyd, K. L., Sleeman, M. W., & Oliver, G. C. (2005) · Nature Genetics · doi:10.1038/ng1642 · Cited by 580 · see citing works
Self-citationInterstitial dendritic cell guidance by haptotactic chemokine gradients
Weber, M., Hauschild, R., Schwarz, J., Moussion, C., de Vries, I., Legler, D. F., Luther, S. A., Bollenbach, T., & Sixt, M. (2013) · Science · doi:10.1126/science.1228456 · Cited by 555 · see citing works
Kida, S., Pantazis, A., & Weller, R. O. (1993) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.1993.tb00476.x · Cited by 520 · see citing works
Chemokine receptor CCR7 required for T lymphocyte exit from peripheral tissues
Debes, G. F., Arnold, C. N., Young, A. J., Krautwald, S., Lipp, M., Hay, J. B., & Butcher, E. C. (2005) · Nature Immunology · doi:10.1038/ni1238 · Cited by 478 · see citing works
Oshio, K., Watanabe, H., Song, Y., Verkman, A. S., & Manley, G. T. (2004) · The FASEB Journal · doi:10.1096/fj.04-1711fje · Cited by 477 · see citing works
Development and plasticity of meningeal lymphatic vessels
Antila, S., Karaman, S., Nurmi, H. J., Airavaara, M., Voutilainen, M. H., Mathivet, T., Chilov, D., Li, Z., Koppinen, T. K., Park, J., et al. (2017) · The Journal of Experimental Medicine · doi:10.1084/jem.20170391 · Cited by 469 · see citing works
PDZ interaction site in ephrinB2 is required for the remodeling of lymphatic vasculaturePreprint
Mäkinen, T., Adams, R. H., Bailey, J., Lü, Q., Ziemiecki, A., Alitalo, K. K., Klein, R., & Wilkinson, G. A. (2005) · Genes & Development · doi:10.1101/gad.330105 · Cited by 461 · see citing works
Cserr, H. F., Harling‐Berg, C. J., & Knopf, P. M. (1992) · Brain Pathology · doi:10.1111/j.1750-3639.1992.tb00703.x · Cited by 450 · see citing works
T cells become licensed in the lung to enter the central nervous system
Odoardi, F., Sie, C., Streyl, K., Ulaganathan, V. K., Schläger, C., Lodygin, D., Heckelsmiller, K., Nietfeld, W., Ellwart, J. W., Klinkert, W. E. F., et al. (2012) · Nature · doi:10.1038/nature11337 · Cited by 440 · see citing works
Multifaceted interactions between adaptive immunity and the central nervous system
Kipnis, J. (2016) · Science · doi:10.1126/science.aag2638 · Cited by 376 · see citing works
Self-citationThe lymphatic system: integral roles in immunity
Randolph, G. J., Ivanov, S., Zinselmeyer, B. H., & Scallan, J. P. (2017) · Annual Review of Immunology · doi:10.1146/annurev-immunol-041015-055354 · Cited by 338 · see citing works
Ajami, B., Samusik, N., Wieghofer, P., Ho, P. P., Crotti, A., Bjornson, Z., Prinz, M., Fantl, W. J., Nolan, G. P., & Steinman, L. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0100-x · Cited by 338 · see citing works
Mora, J. R., Cheng, G., Picarella, D., Briskin, M., Buchanan, N. M., & von Andrian, U. H. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20041645 · Cited by 309 · see citing works
Nerve fibres and their terminals of the dura mater encephali of the rat
Andres, K. H., D�ring, M., Muszynski, K., & Schmidt, R. F. (1987) · Anatomy and Embryology · doi:10.1007/bf00309843 · Cited by 289 · see citing works
Neuronal plasticity and neurotrophic factors in drug responses
Castrén, E., & Antila, H. (2017) · Molecular Psychiatry · doi:10.1038/mp.2017.61 · Cited by 284 · see citing works
Hennet, T., Hagen, F. K., Tabak, L. A., & Marth, J. D. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.26.12070 · Cited by 271 · see citing works
Inflammation-associated lymphangiogenesis: a double-edged sword?
Kim, H., Kataru, R. P., & Koh, G. Y. (2014) · Journal of Clinical Investigation · doi:10.1172/jci71607 · Cited by 227 · see citing works
Kamphorst, A. O., Guermonprez, P., Dudziak, D., & Nussenzweig, M. C. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.1001205 · Cited by 208 · see citing works
Pertussis toxin inhibits migration of B and T lymphocytes into splenic white pulp cords.
Cyster, J. G., & Goodnow, C. C. (1995) · The Journal of Experimental Medicine · doi:10.1084/jem.182.2.581 · Cited by 182 · see citing works
Proescholdt, M. A., Jacobson, S., Tresser, N. J., Oldfield, E. H., & Merrill, M. J. (2002) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/61.10.914 · Cited by 180 · see citing works
Frye, M., Taddei, A., Dierkes, C., Martinez-Corral, I., Fielden, M., Ortsäter, H., Kazenwadel, J., Calado, D. P., Ostergaard, P., Salminen, M., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-03959-6 · Cited by 169 · see citing works
Thrombospondin 1 inhibits inflammatory lymphangiogenesis by CD36 ligation on monocytes
Cursiefen, C., Maruyama, K., Bock, F., Saban, D. R., Sadrai, Z., Lawler, J., Dana, R., & Masli, S. (2011) · The Journal of Experimental Medicine · doi:10.1084/jem.20092277 · Cited by 160 · see citing works
Matrix Stiffness Regulates Endothelial Cell Proliferation through Septin 9
Yeh, Y.-T., Hur, S. S., Chang, J., Wang, K.-C., Chiu, J., Li, Y.-S. J., & Chien, S. (2012) · PLoS ONE · doi:10.1371/journal.pone.0046889 · Cited by 157 · see citing works
Micro RNA regulation of T‐cell differentiation and function
Jeker, L. T., & Bluestone, J. A. (2013) · Immunological Reviews · doi:10.1111/imr.12061 · Cited by 152 · see citing works
van Zwam, M., Huizinga, R., Heijmans, N., van Meurs, M., Wierenga‐Wolf, A. F., Melief, M., Hintzen, R. Q., Hart, B. A. ‘., Amor, S., Boven, L. A., et al. (2008) · The Journal of Pathology · doi:10.1002/path.2476 · Cited by 151 · see citing works
Prox1 expression patterns in the developing and adult murine brain
Lavado, A., & Oliver, G. C. (2006) · Developmental Dynamics · doi:10.1002/dvdy.21024 · Cited by 146 · see citing works
Self-citationJurisic, G., Hajjami, H. M.-E., Karaman, S., Ochsenbein, A. M., Alitalo, A. K., Siddiqui, S. S., Pereira, C. O., Petrova, T. V., & Detmar, M. J. (2012) · Circulation Research · doi:10.1161/circresaha.112.269399 · Cited by 141 · see citing works
Nowotschin, S., & Hadjantonakis, A. (2009) · BMC Developmental Biology · doi:10.1186/1471-213x-9-49 · Cited by 137 · see citing works
Furtado, G. C., Marcondes, M. C. G., Latkowski, J.-A. M., Tsai, J., Wensky, A. K., & Lafaille, J. J. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.181.7.4648 · Cited by 136 · see citing works
Mollanji, R., Bozanovic-Sosic, R., Zakharov, A., Makarian, L., & Johnston, M. G. (2002) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00695.2001 · Cited by 133 · see citing works
Richards, D. F., Fernandez, M., Caulfield, J., & Hawrylowicz, C. M. (2000) · European Journal of Immunology · doi:10.1002/1521-4141(2000)30:8 · Cited by 133 · see citing works
Photodynamic Ablation of Lymphatic Vessels and Intralymphatic Cancer Cells Prevents Metastasis
Tammela, T., Saaristo, A. M., Holopainen, T., Ylä‐Herttuala, S., Andersson, L. C., Virolainen, S., Immonen, I. J. R., & Alitalo, K. K. (2011) · Science Translational Medicine · doi:10.1126/scitranslmed.3001699 · Cited by 120 · see citing works
Ultrasound-aided Multi-parametric Photoacoustic Microscopy of the Mouse Brain
Ning, B., Sun, N., Cao, R., Chen, R., Shung, K. K., Hossack, J. A., Lee, J., Zhou, Q., & Hu, S. (2015) · Scientific Reports · doi:10.1038/srep18775 · Cited by 99 · see citing works
Self-citationZiarek, J. J., Kleist, A. B., London, N., Raveh, B., Montpas, N., Bonneterre, J., St‐Onge, G., DiCosmo-Ponticello, C. J., Koplinski, C. A., Roy, I., et al. (2017) · Science Signaling · doi:10.1126/scisignal.aah5756 · Cited by 96 · see citing works
NEW CONTRIBUTIONS TO THE ANATOMICAL CONNECTIONS OF THE BRAIN AND THE LYMPHATIC SYSTEM
Földi, M., Gellért, A., Kozma, M., et al. (2008) · Acta Anatomica · doi:10.1159/000142849 · Cited by 77 · see citing works
Zozulya, A. L., Ortler, S., Lee, J., Weidenfeller, C., Sándor, M., Wiendl, H., & Fábry, Z. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.2199-08.2009 · Cited by 69 · see citing works
Engels, K., Fox, S. B., Whitehouse, R. M., Gatter, K. C., & Harris, A. L. (1997) · The Journal of Pathology · doi:10.1002/(sici)1096-9896(199708)182:4 · Cited by 60 · see citing works
Go, K. G., Houthoff, H.-J., Hartsuiker, J., BLAAUW, E. H., & Havinga, P. (1986) · Journal of neurosurgery · doi:10.3171/jns.1986.65.5.0642 · Cited by 59 · see citing works
CCR7 deficient inflammatory Dendritic Cells are retained in the Central Nervous System
Clarkson, B. D. S., Walker, A. J., Harris, M. G., Rayasam, A., Hsu, M., Sándor, M., & Fábry, Z. (2017) · Scientific Reports · doi:10.1038/srep42856 · Cited by 58 · see citing works
Effect of AlCl3 and other acids on cerebrospinal fluid production: a correction.
VOGH, B. P., GODMAN, D. R., & Maren, T. H. (1987) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)39243-8 · Cited by 40 · see citing works
Coles, J. A., Myburgh, E., Ritchie, R., Hamilton, A., Rodgers, J., Mottram, J. C., Barrett, M. P., & Brewer, J. M. (2015) · PLoS neglected tropical diseases · doi:10.1371/journal.pntd.0003714 · Cited by 39 · see citing works
NOD2 regulates CXCR3-dependent CD8+ T cell accumulation in intestinal tissues with acute injury
Wu, X.-X., Lahiri, A., Haines, G., Flavell, R., & Abraham, C. (2014) · Journal of Immunology · doi:10.4049/jimmunol.1302436 · Cited by 33 · see citing works
Kilarski, W. W., Muchowicz, A., Wachowska, M., Mężyk-Kopeć, R., Gołąb, J., Swartz, M. A., & Nowak-Sliwinska, P. M. (2013) · Angiogenesis · doi:10.1007/s10456-013-9365-6 · Cited by 31 · see citing works
Venous outflow of the brain after bilateral complete jugular ligation.
Ensarı, S., Kaptanoğlu, E., Tun, K., Gün, T., Beşkonaklı, E., Çelikkanat, S., Dere, H., & Cekirge, S. H. (2008) · PubMed · Cited by 26 · see citing works
Cai, R., Pan, C., Ghasemigharagoz, A., Todorov, M. I., Förstera, B., Zhao, S., Bhatia, H. S., Mrowka, L., Theodorou, D., Rempfler, M., et al. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/374785 · Cited by 18 · see citing works
Wachowska, M., Osiak, A., Muchowicz, A., Gabrysiak, M., Domagała, A., Kilarski, W. W., & Gołąb, J. (2016) · Photodiagnosis and Photodynamic Therapy · doi:10.1016/j.pdpdt.2016.02.004 · Cited by 15 · see citing works
Guan, Y. A., Zhang, Z., Yu, C., Ma, L., Hu, W., Xu, L., Gao, J., Chung, C., Wang, L., Yang, Z., et al. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1003399 · Cited by 12 · see citing works
Effect of internal jugular vein ligation on resorption of cerebrospinal fluid
KAWAJIRI, H., Furuse, M., Namba, R., et al. (1983) · Journal of Maxillofacial Surgery · doi:10.1016/s0301-0503(83)80010-1 · Cited by 11 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Perivascular spaces in the brain: anatomy, physiology and pathology
Wardlaw, J. M., Benveniste, H., Nedergaard, M., Zlokovic, B. V., Mestre, H., Lee, H., Doubal, F. N., Brown, R., Ramirez, J., MacIntosh, B. J., et al. (2020) · Nature Reviews Neurology · doi:10.1038/s41582-020-0312-z · Cited by 870 · see citing works
Meningeal lymphatic vessels at the skull base drain cerebrospinal fluid
Ahn, J. H., Cho, H., Kim, J.-H., Kim, S. H., Ham, J.-S., Park, I., Suh, S. H., Hong, S. P., Song, J.-H., Hong, Y.-K., et al. (2019) · Nature · doi:10.1038/s41586-019-1419-5 · Cited by 811 · see citing works
Functional characterization of the dural sinuses as a neuroimmune interface
Rustenhoven, J., Drieu, A., Mamuladze, T., de Lima, K. A., Dykstra, T., Wall, M., Papadopoulos, Z., Kanamori, M., Salvador, A. F., Baker, W., et al. (2021) · Cell · doi:10.1016/j.cell.2020.12.040 · Cited by 685 · see citing works
Self-citationPombo Antunes, A. R., Scheyltjens, I., Lodi, F., Messiaen, J., Antoranz, A., Duerinck, J., Kancheva, D., Martens, L., De Vlaminck, K., Van Hove, H., et al. (2021) · Nature Neuroscience · doi:10.1038/s41593-020-00789-y · Cited by 704 · see citing works
Skull and vertebral bone marrow are myeloid cell reservoirs for the meninges and CNS parenchyma
Cugurra, A., Mamuladze, T., Rustenhoven, J., Dykstra, T., Beroshvili, G., Greenberg, Z. J., Baker, W., Papadopoulos, Z., Drieu, A., Blackburn, S., et al. (2021) · Science · doi:10.1126/science.abf7844 · Cited by 681 · see citing works
Self-citationHeterogeneity of meningeal B cells reveals a lymphopoietic niche at the CNS borders
Brioschi, S., Wang, W.-L., Peng, V., Wang, M., Shchukina, I., Greenberg, Z. J., Bando, J. K., Jaeger, N., Czepielewski, R. S., Swain, A., et al. (2021) · Science · doi:10.1126/science.abf9277 · Cited by 472 · see citing works
Self-citationParkinson disease and the immune system - Associations, mechanisms and therapeutics
Tan, E.-K., Chao, Y.-X., West, A., Chan, L.-L., Poewe, W., & Jankovic, J. (2020) · Nature Reviews Neurology · doi:10.1038/s41582-020-0344-4 · Cited by 457 · see citing works
Meningeal lymphatics affect microglia responses and anti-Aβ immunotherapy
Da Mesquita, S., Papadopoulos, Z., Dykstra, T., Brase, L., Farias, F. G., Wall, M., Jiang, H., Kodira, C. D., de Lima, K. A., Herz, J., et al. (2021) · Nature · doi:10.1038/s41586-021-03489-0 · Cited by 431 · see citing works
Self-citationMeningeal γδ T cells regulate anxiety-like behavior via IL-17a signaling in neurons
Alves de Lima, K., Rustenhoven, J., Da Mesquita, S., Wall, M., Salvador, A. F., Smirnov, I., Martelossi Cebinelli, G., Mamuladze, T., Baker, W., Papadopoulos, Z., et al. (2020) · Nature Immunology · doi:10.1038/s41590-020-0776-4 · Cited by 416 · see citing works
Self-citationMeningeal lymphatic dysfunction exacerbates traumatic brain injury pathogenesis.
Bolte, A. C., Dutta, A. B., Hurt, M. E., Smirnov, I., Kovacs, M. A., McKee, C. A., Ennerfelt, H. E., Shapiro, D., Nguyen, B. H., Frost, E. L., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-18113-4 · Cited by 357 · see citing works
Alves de Lima, K., Rustenhoven, J., & Kipnis, J. (2020) · Annual Review of Immunology · doi:10.1146/annurev-immunol-102319-103410 · Cited by 348 · 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
Immune cells and CNS physiology: Microglia and beyond
Norris, G. T., & Kipnis, J. (2019) · Journal of Experimental Medicine · doi:10.1084/jem.20180199 · Cited by 274 · see citing works
Self-citationMeningeal lymphatics clear erythrocytes that arise from subarachnoid hemorrhage.
Chen, J., Wang, L., Xu, H., Xing, L., Zhuang, Z., Zheng, Y., Li, X., Wang, C., Chen, S., Guo, Z., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-16851-z · Cited by 208 · see citing works
Da Mesquita, S., Herz, J., Wall, M., Dykstra, T., de Lima, K. A., Norris, G. T., Dabhi, N., Kennedy, T., Baker, W., & Kipnis, J. (2021) · Science Advances · doi:10.1126/sciadv.abe4601 · Cited by 172 · see citing works
Self-citationAltered gut microbiota associated with symptom severity in schizophrenia
Li, S., Zhuo, M., Huang, X., Huang, Y., Zhou, J., Xiong, D., Li, J., Liu, Y., Pan, Z., Li, H., et al. (2020) · PeerJ · doi:10.7717/peerj.9574 · Cited by 142 · see citing works
Anatomy and function of the vertebral column lymphatic network in mice
Jacob, L., Boisserand, L. S. B., Geraldo, L. H. M., de Brito Neto, J., Mathivet, T., Antila, S., Barka, B., Xu, Y., Thomas, J.-M., Pestel, J., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-12568-w · Cited by 144 · see citing works
Clearance of cerebrospinal fluid from the sacral spine through lymphatic vessels
Ma, Q., Decker, Y., Müller, A., Ineichen, B. V., & Proulx, S. T. (2019) · Journal of Experimental Medicine · doi:10.1084/jem.20190351 · Cited by 136 · see citing works
Chronic inflammation in multiple sclerosis - seeing what was always there
Matthews, P. M. (2019) · Nature Reviews Neurology · doi:10.1038/s41582-019-0240-y · Cited by 128 · see citing works
Living on the Edge of the CNS: Meninges Cell Diversity in Health and Disease
Derk, J., Jones, H. E., Como, C., Pawlikowski, B., & Siegenthaler, J. A. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.703944 · Cited by 120 · see citing works
Impaired meningeal lymphatic vessel development worsens stroke outcome.
Yanev, P., Poinsatte, K., Hominick, D., Khurana, N., Zuurbier, K. R., Berndt, M., Plautz, E. J., Dellinger, M. T., & Stowe, A. M. (2020) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x18822921 · Cited by 126 · see citing works
Glymphatics visualization after focused ultrasound-induced blood-brain barrier opening in humans
Meng, Y., Abrahao, A., Heyn, C. C., Bethune, A. J., Huang, Y., Pople, C. B., Aubert, I., Hamani, C., Zinman, L., Hynynen, K., et al. (2019) · Annals of Neurology · doi:10.1002/ana.25604 · Cited by 114 · see citing works
Quantum effects in the brain: A review
Adams, B., & Petruccione, F. (2020) · AVS Quantum Science · doi:10.1116/1.5135170 · Cited by 80 · see citing works
Basal lamina changes in neurodegenerative disorders
Nguyen, B., Bix, G., & Yao, Y. (2021) · Molecular Neurodegeneration · doi:10.1186/s13024-021-00502-y · Cited by 75 · see citing works
Dissecting the human leptomeninges at single-cell resolution
Kearns, N. A., Iatrou, A., Flood, D. J., De Tissera, S., Mullaney, Z. M., Xu, J., Gaiteri, C., Bennett, D. A., & Wang, Y. (2023) · Nature Communications · doi:10.1038/s41467-023-42825-y · Cited by 75 · see citing works
Immunological defense of CNS barriers against infections
Ampie, L., & McGavern, D. B. (2022) · Immunity · doi:10.1016/j.immuni.2022.04.012 · Cited by 63 · see citing works
Meningeal mast cells as key effectors of stroke pathology.
Arac, A., Grimbaldeston, M. A., Galli, S. J., Bliss, T. M., & Steinberg, G. K. (2019) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2019.00126 · Cited by 37 · see citing works
Lymphatic Capillaries in Aging
Jakic, B., Kerjaschki, D., & Wick, G. (2020) · Gerontology · doi:10.1159/000508459 · Cited by 28 · see citing works
Dong, H., Dai, X., Zhou, Y., Shi, C., Bhuiyan, P., Sun, Z., Li, N., & Jin, W. (2024) · Journal of Neuroinflammation · doi:10.1186/s12974-024-03028-4 · Cited by 27 · see citing works
The brain washing system in sepsis-associated encephalopathy
Chen, T., Hu, J., Liao, Y., Xie, S., & Zhang, L. (2025) · Journal of Neuroinflammation · doi:10.1186/s12974-025-03602-4 · Cited by 8 · see citing works
- Authors
- Louveau, A., Herz, J., Alme, M. N., Salvador, A. F., Dong, M. Q., Viar, K. E., Herod, S. G., Knopp, J., Setliff, J. C., Lupi, A. L., Da Mesquita, S., Frost, E. L., Gaultier, A., Harris, T. H., Cao, R., Hu, S., Lukens, J. R., Smirnov, I., Overall, C. C., Oliver, G., & Kipnis, J.
- Affiliations
- University of Virginia (US)
- Haukeland University Hospital (NO)
- Northwestern University (US)
- University Medical Center of the Johannes Gutenberg University Mainz (DE)
- Corresponding author
- Louveau, Antoine
- Kipnis, Jonathan
- ORCID
- Venue
- Nature Neuroscience
- Published
- 2018-09-17
- Volume
- 21
- Issue
- 10
- Pages
- 1380-1391
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC6214619
- OpenAlex
- W2892318814
- Cited by
- 956
- References
- 61
- Citations by year
- 2026: 110 · 2025: 128 · 2024: 143 · 2023: 143 · 2022: 132 · 2021: 145 · 2020: 91 · 2019: 57 · 2018: 6
- FWCI
- 28.03
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (5r01hl073402-19)
- National Institute on Aging (R01AG034113, R37AG034113)
- National Heart, Lung, and Blood Institute (R01-HL073402)
- National Institute of Neurological Disorders and Stroke (R01NS096967)
- Topics
- Health Sciences › Medicine › Oncology › Lymphatic System and Diseases
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Cerebrospinal fluid and hydrocephalus
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Keywords
- meningeal lymphatic vessels, lymphatic drainage, neuroinflammation, multiple sclerosis, cerebrospinal fluid, CCR7, lymphatic endothelial cells, autoreactive T cells, lymph node drainage, central nervous system autoimmunity
- MeSH terms
- Prospero-Related Homeobox 1 Protein, Animals, Central Nervous System, Dendritic Cells, Disease Models, Animal, Encephalitis, Lymph Nodes, Male, Meninges, Mice, Inbred C57BL, Mice, Transgenic, Peptide Fragments, Spleen, T-Lymphocytes, Antigens, CD, Photosensitizing Agents, Homeodomain Proteins, Tumor Suppressor Proteins, MicroRNAs, Lymphatic Vessels, Green Fluorescent Proteins, Mice, Receptors, CCR7, Myelin-Oligodendrocyte Glycoprotein
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
