Louveau, A. et al. Structural and functional features of central nervous system lymphatic vessels. Nature 523, 337–341 (2015).
Kida, S., Pantazis, A. & Weller, R. O. CSF drains directly from the subarachnoid space into nasal lymphatics in the rat. Anatomy, histology and immunological significance. Neuropathol. Appl. Neurobiol. 19, 480–488 (1993).
Cserr, H. F., Harling-Berg, C. J. & Knopf, P. M. Drainage of brain extracellular fluid into blood and deep cervical lymph and its immunological significance. Brain. Pathol. 2, 269–276 (1992).
Iliff, J. J. et al. A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid β. Sci. Transl. Med. 4, 147ra111 (2012).
Go, K. G., Houthoff, H. J., Hartsuiker, J., Blaauw, E. H. & Havinga, P. Fluid secretion in arachnoid cysts as a clue to cerebrospinal fluid absorption at the arachnoid granulation. J. Neurosurg. 65, 642–648 (1986).
Ma, Q., Ineichen, B. V., Detmar, M. & Proulx, S. T. Outflow of cerebrospinal fluid is predominantly through lymphatic vessels and is reduced in aged mice. Nat. Commun. 8, 1434 (2017).
Kipnis, J. Multifaceted interactions between adaptive immunity and the central nervous system. Science 353, 766–771 (2016).
Aspelund, A. et al. A dural lymphatic vascular system that drains brain interstitial fluid and macromolecules. J. Exp. Med. 212, 991–999 (2015).
Engelhardt, B., Vajkoczy, P. & Weller, R. O. The movers and shapers in immune privilege of the CNS. Nat. Immunol. 18, 123–131 (2017).
Louveau, A. et al. Understanding the functions and relationships of the glymphatic system and meningeal lymphatics. J. Clin. Invest. 127, 3210–3219 (2017).
Andres, K. H., von Düring, M., Muszynski, K. & Schmidt, R. F. Nerve fibres and their terminals of the dura mater encephali of the rat. Anat. Embryol. (Berl.) 175, 289–301 (1987).
Absinta, M. et al. Human and nonhuman primate meninges harbor lymphatic vessels that can be visualized noninvasively by MRI. eLife 6, e29738 (2017).
Kamphorst, A. O., Guermonprez, P., Dudziak, D. & Nussenzweig, M. C. Route of antigen uptake differentially impacts presentation by dendritic cells and activated monocytes. J. Immunol. 185, 3426–3435 (2010).
Baluk, P. et al. Functionally specialized junctions between endothelial cells of lymphatic vessels. J. Exp. Med. 204, 2349–2362 (2007).
Castrén, E. & Antila, H. Neuronal plasticity and neurotrophic factors in drug responses. Mol. Psychiatry 22, 1085–1095 (2017).
Földi, M. et al. New contributions to the anatomical connections of the brain and the lymphatic system. Acta Anat. 64, 498–505 (1966).
Antila, S. et al. Development and plasticity of meningeal lymphatic vessels. J. Exp. Med. 214, 3645–3667 (2017).
Hennet, T., Hagen, F. K., Tabak, L. A. & Marth, J. D. T-cell-specific deletion of a polypeptide N-acetylgalactosaminyl-transferase gene by site-directed recombination. Proc. Natl. Acad. Sci. USA 92, 12070–12074 (1995).
Derecki, N. C. et al. Regulation of learning and memory by meningeal immunity: a key role for IL-4. J. Exp. Med. 207, 1067–1080 (2010).
Ziarek, J. J. et al. Structural basis for chemokine recognition by a G protein-coupled receptor and implications for receptor activation. Sci. Signal. 10, eaah5756 (2017).
Debes, G. F. et al. Chemokine receptor CCR7 required for T lymphocyte exit from peripheral tissues. Nat. Immunol. 6, 889–894 (2005).
Weber, M. et al. Interstitial dendritic cell guidance by haptotactic chemokine gradients. Science 339, 328–332 (2013).
Randolph, G. J., Ivanov, S., Zinselmeyer, B. H. & Scallan, J. P. The lymphatic system: integral roles in immunity. Annu. Rev. Immunol. 35, 31–52 (2017).
Clarkson, B. D. et al. CCR7 deficient inflammatory dendritic cells are retained in the central nervous system. Sci. Rep. 7, 42856 (2017).
Wigle, J. T. & Oliver, G. Prox1 function is required for the development of the murine lymphatic system. Cell 98, 769–778 (1999).
Harvey, N. L. et al. Lymphatic vascular defects promoted by Prox1 haploinsufficiency cause adult-onset obesity. Nat. Genet. 37, 1072–1081 (2005).
Lavado, A. & Oliver, G. Prox1 expression patterns in the developing and adult murine brain. Dev. Dyn. 236, 518–524 (2007).
Tammela, T. et al. Photodynamic ablation of lymphatic vessels and intralymphatic cancer cells prevents metastasis. Sci. Transl. Med. 3, 69ra11 (2011).
Kim, H., Kataru, R. P. & Koh, G. Y. Inflammation-associated lymphangiogenesis: a double-edged sword? J. Clin. Invest. 124, 936–942 (2014).
Dendrou, C. A., Fugger, L. & Friese, M. A. Immunopathology of multiple sclerosis. Nat. Rev. Immunol. 15, 545–558 (2015).
Ajami, B. et al. Single-cell mass cytometry reveals distinct populations of brain myeloid cells in mouse neuroinflammation and neurodegeneration models. Nat. Neurosci. 21, 541–551 (2018).
Proescholdt, M. A., Jacobson, S., Tresser, N., Oldfield, E. H. & Merrill, M. J. Vascular endothelial growth factor is expressed in multiple sclerosis plaques and can induce inflammatory lesions in experimental allergic encephalomyelitis rats. J. Neuropathol. Exp. Neurol. 61, 914–925 (2002).
Cursiefen, C. et al. Thrombospondin 1 inhibits inflammatory lymphangiogenesis by CD36 ligation on monocytes. J. Exp. Med. 208, 1083–1092 (2011).
Jurisic, G. et al. An unexpected role of semaphorin3a-neuropilin-1 signaling in lymphatic vessel maturation and valve formation. Circ. Res. 111, 426–436 (2012).
Mäkinen, T. et al. PDZ interaction site in ephrinB2 is required for the remodeling of lymphatic vasculature. Genes Dev. 19, 397–410 (2005).
Frye, M. et al. Matrix stiffness controls lymphatic vessel formation through regulation of a GATA2-dependent transcriptional program. Nat. Commun. 9, 1511 (2018).
Yeh, Y. T. et al. Matrix stiffness regulates endothelial cell proliferation through septin 9. PLoS One 7, e46889 (2012).
Furtado, G. C. et al. Swift entry of myelin-specific T lymphocytes into the central nervous system in spontaneous autoimmune encephalomyelitis. J. Immunol. 181, 4648–4655 (2008).
Phillips, M. J., Needham, M. & Weller, R. O. Role of cervical lymph nodes in autoimmune encephalomyelitis in the Lewis rat. J. Pathol. 182, 457–464 (1997).
van Zwam, M. et al. Surgical excision of CNS-draining lymph nodes reduces relapse severity in chronic-relapsing experimental autoimmune encephalomyelitis. J. Pathol. 217, 543–551 (2009).
Rottman, J. B. et al. Leukocyte recruitment during onset of experimental allergic encephalomyelitis is CCR1 dependent. Eur. J. Immunol. 30, 2372–2377 (2000).
Guan, Y. J. et al. Phospho-SXXE/D motif mediated TNF receptor 1-TRADD death domain complex formation for T cell activation and migration. J. Immunol. 187, 1289–1297 (2011).
Wu, X., Lahiri, A., Haines, G. K. III, Flavell, R. A. & Abraham, C. NOD2 regulates CXCR3-dependent CD8 + T cell accumulation in intestinal tissues with acute injury. J. Immunol. 192, 3409–3418 (2014).
Jeker, L. T. & Bluestone, J. A. MicroRNA regulation of T-cell differentiation and function. Immunol. Rev. 253, 65–81 (2013).
Brinker, T., Stopa, E., Morrison, J. & Klinge, P. A new look at cerebrospinal fluid circulation. Fluids Barriers CNS 11, 10 (2014).
Cai, R. et al. Panoptic vDISCO imaging reveals neuronal connectivity, remote trauma effects and meningeal vessels in intact transparent mice. Preprint at bioRxiv https://doi.org/10.1101/374785 (2018).
Mollanji, R., Bozanovic-Sosic, R., Zakharov, A., Makarian, L. & Johnston, M. G. Blocking cerebrospinal fluid absorption through the cribriform plate increases resting intracranial pressure. Am. J. Physiol. Regul. Integr. Comp. Physiol. 282, R1593–R1599 (2002).
Odoardi, F. et al. T cells become licensed in the lung to enter the central nervous system. Nature 488, 675–679 (2012).
Mora, J. R. et al. Reciprocal and dynamic control of CD8 T cell homing by dendritic cells from skin- and gut-associated lymphoid tissues. J. Exp. Med. 201, 303–316 (2005).
Zozulya, A. L. et al. Intracerebral dendritic cells critically modulate encephalitogenic versus regulatory immune responses in the CNS. J. Neurosci. 29, 140–152 (2009).
Kilarski, W. W. et al. Optimization and regeneration kinetics of lymphatic-specific photodynamic therapy in the mouse dermis. Angiogenesis 17, 347–357 (2014).
Wachowska, M. et al. Investigation of cell death mechanisms in human lymphatic endothelial cells undergoing photodynamic therapy. Photodiagnosis Photodyn. Ther. 14, 57–65 (2016).
Ensari, S. et al. Venous outflow of the brain after bilateral complete jugular ligation. Turk. Neurosurg. 18, 56–60 (2008).
Kawajiri, H., Furuse, M., Namba, R., Kotani, J. & Oka, T. Effect of internal jugular vein ligation on resorption of cerebrospinal fluid. J. Maxillofac. Surg. 11, 42–45 (1983).
Vogh, B. P., Godman, D. R. & Maren, T. H. Effect of AlCl3 and other acids on cerebrospinal fluid production: a correction. J. Pharmacol. Exp. Ther. 243, 35–39 (1987).
Ning, B. et al. Ultrasound-aided multi-parametric photoacoustic microscopy of the mouse brain. Sci. Rep. 5, 18775 (2015).
Coles, J. A. et al. Intravital imaging of a massive lymphocyte response in the cortical dura of mice after peripheral infection by trypanosomes. PLoS Negl. Trop. Dis. 9, e0003714 (2015).
Nowotschin, S. & Hadjantonakis, A. K. Use of KikGR a photoconvertible green-to-red fluorescent protein for cell labeling and lineage analysis in ES cells and mouse embryos. BMC Dev. Biol. 9, 49 (2009).
Oshio, K., Watanabe, H., Song, Y., Verkman, A. S. & Manley, G. T. Reduced cerebrospinal fluid production and intracranial pressure in mice lacking choroid plexus water channel Aquaporin-1. FASEB J. 19, 76–78 (2005).
Cyster, J. G. & Goodnow, C. C. Pertussis toxin inhibits migration of B and T lymphocytes into splenic white pulp cords. J. Exp. Med. 182, 581–586 (1995).
Da Mesquita, S. et al. Functional aspects of meningeal lymphatics in ageing and Alzheimer’s disease. Nature 560, 185–191 (2018).