{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T23:31:24Z","timestamp":1794007884530,"version":"4.8.0"},"reference-count":100,"publisher":"Springer Science and Business Media LLC","issue":"10","license":[{"start":{"date-parts":[[2025,5,2]],"date-time":"2025-05-02T00:00:00Z","timestamp":1746144000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2025,5,2]],"date-time":"2025-05-02T00:00:00Z","timestamp":1746144000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Rev Immunol"],"published-print":{"date-parts":[[2025,10]]},"DOI":"10.1038\/s41577-025-01175-0","type":"journal-article","created":{"date-parts":[[2025,5,2]],"date-time":"2025-05-02T07:55:39Z","timestamp":1746172539000},"page":"766-775","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":97,"title":["Redefining CNS immune privilege"],"prefix":"10.1038","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9861-3574","authenticated-orcid":false,"given":"Leon C. D.","family":"Smyth","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3714-517X","authenticated-orcid":false,"given":"Jonathan","family":"Kipnis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,5,2]]},"reference":[{"key":"1175_CR1","first-page":"14","volume":"1","author":"Y Shirai","year":"1921","unstructured":"Shirai, Y. On the transplantation of the rat sarcoma in adult heterogenous animals. Jpn. Med. World 1, 14\u201315 (1921).","journal-title":"Jpn. Med. World"},{"key":"1175_CR2","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1084\/jem.38.2.183","volume":"38","author":"JB Murphy","year":"1923","unstructured":"Murphy, J. B. & Sturm, E. Conditions determining the transplantability of tissues in the brain. J. Exp. Med. 38, 183\u2013197 (1923).","journal-title":"J. Exp. Med."},{"key":"1175_CR3","first-page":"58","volume":"29","author":"PB Medawar","year":"1948","unstructured":"Medawar, P. B. Immunity to homologous grafted skin. III. The fate of skin homographs transplanted to the brain, to subcutaneous tissue, and to the anterior chamber of the eye. Br. J. Exp. Pathol. 29, 58\u201369 (1948).","journal-title":"Br. J. Exp. Pathol."},{"key":"1175_CR4","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.1097\/00007890-196711000-00012","volume":"5","author":"EM Lance","year":"1967","unstructured":"Lance, E. M. A functional and morphological study of intracranial parathyroid allografts in the dog. Transplantation 5, 1471 (1967).","journal-title":"Transplantation"},{"key":"1175_CR5","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1001\/archsurg.1966.01320230126023","volume":"92","author":"MA Block","year":"1966","unstructured":"Block, M. A., Tworek, E. J. & Miller, J. M. Parathyroid homografts in brain tissue: experimental studies. Arch. Surg. 92, 778\u2013784 (1966).","journal-title":"Arch. Surg."},{"key":"1175_CR6","doi-asserted-by":"crossref","first-page":"136","DOI":"10.3389\/fnmol.2018.00136","volume":"11","author":"N Fainstein","year":"2018","unstructured":"Fainstein, N. & Ben-Hur, T. Brain region-dependent rejection of neural precursor cell transplants. Front. Mol. Neurosci. 11, 136 (2018).","journal-title":"Front. Mol. Neurosci."},{"key":"1175_CR7","doi-asserted-by":"crossref","first-page":"2483","DOI":"10.1634\/stemcells.2006-0174","volume":"24","author":"TM Coyne","year":"2006","unstructured":"Coyne, T. M., Marcus, A. J., Woodbury, D. & Black, I. B. Marrow stromal cells transplanted to the adult brain are rejected by an inflammatory response and transfer donor labels to host neurons and glia. Stem Cell 24, 2483\u20132492 (2006).","journal-title":"Stem Cell"},{"key":"1175_CR8","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/0306-4522(90)90413-X","volume":"37","author":"JM Lawrence","year":"1990","unstructured":"Lawrence, J. M., Morris, R. J., Wilson, D. J. & Raisman, G. Mechanisms of allograft rejection in the rat brain. Neuroscience 37, 431\u2013462 (1990).","journal-title":"Neuroscience"},{"key":"1175_CR9","doi-asserted-by":"crossref","first-page":"100813","DOI":"10.1016\/j.isci.2019.100813","volume":"23","author":"N Hoffmann","year":"2019","unstructured":"Hoffmann, N. et al. A xenotransplant model of human brain tumors in wild-type mice. iScience 23, 100813 (2019).","journal-title":"iScience"},{"key":"1175_CR10","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.it.2006.11.004","volume":"28","author":"I Galea","year":"2007","unstructured":"Galea, I., Bechmann, I. & Perry, V. H. What is immune privilege (not)? Trends Immunol. 28, 12\u201318 (2007).","journal-title":"Trends Immunol."},{"key":"1175_CR11","unstructured":"Mascagni, P. Vasorum Lymphaticorum Corporis Humani Historia et Ichnographia (Pazzini Carli, 1787)."},{"key":"1175_CR12","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1007\/BF00309843","volume":"175","author":"KH Andres","year":"1987","unstructured":"Andres, K. H., von D\u00fcring, M., Muszynski, K. & Schmidt, R. F. Nerve fibres and their terminals of the dura mater encephali of the rat. Anat. Embryol. 175, 289\u2013301 (1987).","journal-title":"Anat. Embryol."},{"key":"1175_CR13","doi-asserted-by":"crossref","first-page":"2110","DOI":"10.1016\/S0140-6736(03)15114-8","volume":"362","author":"IK Luki\u0107","year":"2003","unstructured":"Luki\u0107, I. K., Glun\u010di\u0107, V., Ivki\u0107, G., Hubenstorf, M. & Maru\u0161i\u0107, A. Virtual dissection: a lesson from the 18th century. Lancet 362, 2110\u20132113 (2003).","journal-title":"Lancet"},{"key":"1175_CR14","unstructured":"Ehrlich, P. Das Sauerstoff-Bed\u00fcrfniss Des Organismus: Eine Farbenanalytische Studie (Verlag von August Hirschwald, 1885)."},{"key":"1175_CR15","unstructured":"Key, A. & Retzius, G. Studien in Der Anatomie Des Nervensystems Und Des Bindegewebes https:\/\/collections.nlm.nih.gov\/catalog\/nlm:nlmuid-66211410RX2-mvpart (Samson & Wallin, 1875)."},{"key":"1175_CR16","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1083\/jcb.34.1.207","volume":"34","author":"TS Reese","year":"1967","unstructured":"Reese, T. S. & Karnovsky, M. J. Fine structural localization of a blood\u2013brain barrier to exogenous peroxidase. J. Cell Biol. 34, 207\u2013217 (1967).","journal-title":"J. Cell Biol."},{"key":"1175_CR17","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1083\/jcb.40.3.648","volume":"40","author":"MW Brightman","year":"1969","unstructured":"Brightman, M. W. & Reese, T. S. Junctions between intimately apposed cell membranes in the vertebrate brain. J. Cell Biol. 40, 648\u2013677 (1969).","journal-title":"J. Cell Biol."},{"key":"1175_CR18","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1002\/cne.901640202","volume":"164","author":"S Nabeshima","year":"1975","unstructured":"Nabeshima, S., Reese, T. S., Landis, D. M. D. & Brightman, M. W. Junctions in the meninges and marginal glia. J. Comp. Neurol. 164, 127\u2013169 (1975).","journal-title":"J. Comp. Neurol."},{"key":"1175_CR19","doi-asserted-by":"crossref","unstructured":"Barker, C. F. & Billingham, R. E. in Advances in Immunology (eds Kunkel, H. G. & Dixon, F. J.) 1\u201354 (Academic Press, 1978).","DOI":"10.1016\/S0065-2776(08)60930-X"},{"key":"1175_CR20","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1038\/s41593-019-0393-4","volume":"22","author":"H Van Hove","year":"2019","unstructured":"Van Hove, H. et al. A single-cell atlas of mouse brain macrophages reveals unique transcriptional identities shaped by ontogeny and tissue environment. Nat. Neurosci. 22, 1021\u20131035 (2019).","journal-title":"Nat. Neurosci."},{"key":"1175_CR21","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.cell.2020.06.039","volume":"182","author":"G Oliver","year":"2020","unstructured":"Oliver, G., Kipnis, J., Randolph, G. J. & Harvey, N. L. The lymphatic vasculature in the 21st century: novel functional roles in homeostasis and disease. Cell 182, 270\u2013296 (2020).","journal-title":"Cell"},{"key":"1175_CR22","doi-asserted-by":"publisher","unstructured":"Smyth, L. C. D., Beschorner, N., Nedergaard, M. & Kipnis, J. Cellular contributions to glymphatic and lymphatic waste clearance in the brain. Cold Spring Harb. Perspect. Biol. https:\/\/doi.org\/10.1101\/cshperspect.a041370 (2024).","DOI":"10.1101\/cshperspect.a041370"},{"key":"1175_CR23","first-page":"21","volume":"31","author":"LH Weed","year":"1914","unstructured":"Weed, L. H. Studies on cerebro-spinal fluid. no. II: the theories of drainage of cerebro-spinal fluid with an analysis of the methods of investigation. J. Med. Res. 31, 21\u201349 (1914).","journal-title":"J. Med. Res."},{"key":"1175_CR24","doi-asserted-by":"crossref","first-page":"2429","DOI":"10.1007\/s00018-020-03706-5","volume":"78","author":"ST Proulx","year":"2021","unstructured":"Proulx, S. T. Cerebrospinal fluid outflow: a review of the historical and contemporary evidence for arachnoid villi, perineural routes, and dural lymphatics. Cell. Mol. Life Sci. 78, 2429\u20132457 (2021).","journal-title":"Cell. Mol. Life Sci."},{"key":"1175_CR25","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1038\/ni.3666","volume":"18","author":"B Engelhardt","year":"2017","unstructured":"Engelhardt, B., Vajkoczy, P. & Weller, R. O. The movers and shapers in immune privilege of the CNS. Nat. Immunol. 18, 123\u2013131 (2017).","journal-title":"Nat. Immunol."},{"key":"1175_CR26","volume":"8","author":"Q Ma","year":"2017","unstructured":"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).","journal-title":"Nat. Commun."},{"key":"1175_CR27","doi-asserted-by":"crossref","first-page":"698865","DOI":"10.3389\/fnagi.2021.698865","volume":"13","author":"M Rado\u0161","year":"2021","unstructured":"Rado\u0161, M., \u017divko, M., Peri\u0161a, A., Ore\u0161kovi\u0107, D. & Klarica, M. No arachnoid granulations\u2014no problems: number, size, and distribution of arachnoid granulations from birth to 80 years of age. Front. Aging Neurosci. 13, 698865 (2021).","journal-title":"Front. Aging Neurosci."},{"key":"1175_CR28","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1038\/s41586-018-0368-8","volume":"560","author":"S Da Mesquita","year":"2018","unstructured":"Da Mesquita, S. et al. Functional aspects of meningeal lymphatics in ageing and Alzheimer\u2019s disease. Nature 560, 185\u2013191 (2018).","journal-title":"Nature"},{"key":"1175_CR29","doi-asserted-by":"crossref","first-page":"147ra111","DOI":"10.1126\/scitranslmed.3003748","volume":"4","author":"JJ Iliff","year":"2012","unstructured":"Iliff, J. J. et al. A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid \u03b2. Sci. Transl. Med. 4, 147ra111\u2013147ra111 (2012).","journal-title":"Sci. Transl. Med."},{"key":"1175_CR30","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1038\/s41586-023-06993-7","volume":"627","author":"LCD Smyth","year":"2024","unstructured":"Smyth, L. C. D. et al. Identification of direct connections between the dura and the brain. Nature 627, 165\u2013173 (2024).","journal-title":"Nature"},{"key":"1175_CR31","doi-asserted-by":"crossref","first-page":"104558","DOI":"10.1016\/j.ebiom.2023.104558","volume":"91","author":"I Spera","year":"2023","unstructured":"Spera, I. et al. Open pathways for cerebrospinal fluid outflow at the cribriform plate along the olfactory nerves. eBioMedicine 91, 104558 (2023).","journal-title":"eBioMedicine"},{"key":"1175_CR32","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1038\/s41590-022-01158-6","volume":"23","author":"M Hsu","year":"2022","unstructured":"Hsu, M. et al. Neuroinflammation creates an immune regulatory niche at the meningeal lymphatic vasculature near the cribriform plate. Nat. Immunol. 23, 581\u2013593 (2022).","journal-title":"Nat. Immunol."},{"key":"1175_CR33","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1007\/s00401-018-1809-z","volume":"135","author":"RO Weller","year":"2018","unstructured":"Weller, R. O., Sharp, M. M., Christodoulides, M., Carare, R. O. & M\u00f8llg\u00e5rd, K. The meninges as barriers and facilitators for the movement of fluid, cells and pathogens related to the rodent and human CNS. Acta Neuropathol. 135, 363\u2013385 (2018).","journal-title":"Acta Neuropathol."},{"key":"1175_CR34","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1016\/j.cell.2020.12.040","volume":"184","author":"J Rustenhoven","year":"2021","unstructured":"Rustenhoven, J. et al. Functional characterization of the dural sinuses as a neuroimmune interface. Cell 184, 1000\u20131016.e27 (2021).","journal-title":"Cell"},{"key":"1175_CR35","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1038\/s41586-019-1419-5","volume":"572","author":"JH Ahn","year":"2019","unstructured":"Ahn, J. H. et al. Meningeal lymphatic vessels at the skull base drain cerebrospinal fluid. Nature 572, 62\u201366 (2019).","journal-title":"Nature"},{"key":"1175_CR36","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1038\/s41586-023-06899-4","volume":"625","author":"J-H Yoon","year":"2024","unstructured":"Yoon, J.-H. et al. Nasopharyngeal lymphatic plexus is a hub for cerebrospinal fluid drainage. Nature 625, 768\u2013777 (2024).","journal-title":"Nature"},{"key":"1175_CR37","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1038\/nature14432","volume":"523","author":"A Louveau","year":"2015","unstructured":"Louveau, A. et al. Structural and functional features of central nervous system lymphatic vessels. Nature 523, 337\u2013341 (2015).","journal-title":"Nature"},{"key":"1175_CR38","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1084\/jem.20142290","volume":"212","author":"A Aspelund","year":"2015","unstructured":"Aspelund, A. et al. A dural lymphatic vascular system that drains brain interstitial fluid and macromolecules. J. Exp. Med. 212, 991\u2013999 (2015).","journal-title":"J. Exp. Med."},{"key":"1175_CR39","doi-asserted-by":"crossref","first-page":"1380","DOI":"10.1038\/s41593-018-0227-9","volume":"21","author":"A Louveau","year":"2018","unstructured":"Louveau, A. et al. CNS lymphatic drainage and neuroinflammation are regulated by meningeal lymphatic vasculature. Nat. Neurosci. 21, 1380\u20131391 (2018).","journal-title":"Nat. Neurosci."},{"key":"1175_CR40","doi-asserted-by":"crossref","DOI":"10.1084\/jem.20241752","volume":"222","author":"Z Papadopoulos","year":"2025","unstructured":"Papadopoulos, Z. et al. Differential impact of lymphatic outflow pathways on cerebrospinal fluid homeostasis. J. Exp. Med. 222, e20241752 (2025).","journal-title":"J. Exp. Med."},{"key":"1175_CR41","doi-asserted-by":"crossref","first-page":"3645","DOI":"10.1084\/jem.20170391","volume":"214","author":"S Antila","year":"2017","unstructured":"Antila, S. et al. Development and plasticity of meningeal lymphatic vessels. J. Exp. Med. 214, 3645\u20133667 (2017).","journal-title":"J. Exp. Med."},{"key":"1175_CR42","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1038\/s41586-019-1912-x","volume":"577","author":"E Song","year":"2020","unstructured":"Song, E. et al. VEGF-C-driven lymphatic drainage enables immunosurveillance of brain tumours. Nature 577, 689\u2013694 (2020).","journal-title":"Nature"},{"key":"1175_CR43","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1038\/s41422-020-0287-8","volume":"30","author":"X Hu","year":"2020","unstructured":"Hu, X. et al. Meningeal lymphatic vessels regulate brain tumor drainage and immunity. Cell Res. 30, 229\u2013243 (2020).","journal-title":"Cell Res."},{"key":"1175_CR44","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1038\/s41586-024-08279-y","volume":"637","author":"MW Kim","year":"2024","unstructured":"Kim, M. W. et al. Endogenous self-peptides guard immune privilege of the central nervous system. Nature 637, 176\u2013183 (2024).","journal-title":"Nature"},{"key":"1175_CR45","first-page":"657","volume":"148","author":"JA MacLean","year":"1996","unstructured":"MacLean, J. A. et al. Sequestration of inhaled particulate antigens by lung phagocytes. A mechanism for the effective inhibition of pulmonary cell-mediated immunity. Am. J. Pathol. 148, 657\u2013666 (1996).","journal-title":"Am. J. Pathol."},{"key":"1175_CR46","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1005044","volume":"11","author":"G Mora-Bau","year":"2015","unstructured":"Mora-Bau, G. et al. Macrophages subvert adaptive immunity to urinary tract infection. PLOS Pathog. 11, e1005044 (2015).","journal-title":"PLOS Pathog."},{"key":"1175_CR47","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1038\/s41586-022-05397-3","volume":"611","author":"A Drieu","year":"2022","unstructured":"Drieu, A. et al. Parenchymal border macrophages regulate the flow dynamics of the cerebrospinal fluid. Nature 611, 585\u2013593 (2022).","journal-title":"Nature"},{"key":"1175_CR48","doi-asserted-by":"crossref","first-page":"2085","DOI":"10.1016\/j.immuni.2022.09.005","volume":"55","author":"K De Vlaminck","year":"2022","unstructured":"De Vlaminck, K. et al. Differential plasticity and fate of brain-resident and recruited macrophages during the onset and resolution of neuroinflammation. Immunity 55, 2085\u20132102.e9 (2022).","journal-title":"Immunity"},{"key":"1175_CR49","doi-asserted-by":"crossref","first-page":"eabe4601","DOI":"10.1126\/sciadv.abe4601","volume":"7","author":"S Da Mesquita","year":"2021","unstructured":"Da Mesquita, S. et al. Aging-associated deficit in CCR7 is linked to worsened glymphatic function, cognition, neuroinflammation, and \u03b2-amyloid pathology. Sci. Adv. 7, eabe4601 (2021).","journal-title":"Sci. Adv."},{"key":"1175_CR50","doi-asserted-by":"crossref","first-page":"eadu2910","DOI":"10.1126\/sciimmunol.adu2910","volume":"10","author":"M Marin-Rodero","year":"2025","unstructured":"Marin-Rodero, M. et al. The meninges host a distinct compartment of regulatory T cells that preserves brain homeostasis. Sci. Immunol.\u00a010, eadu2910 (2025).","journal-title":"Sci. Immunol."},{"key":"1175_CR51","doi-asserted-by":"crossref","first-page":"4946","DOI":"10.1016\/j.cell.2024.07.002","volume":"187","author":"H Xu","year":"2024","unstructured":"Xu, H. et al. The choroid plexus synergizes with immune cells during neuroinflammation. Cell 187, 4946\u20134963.e17 (2024).","journal-title":"Cell"},{"key":"1175_CR52","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1038\/nature08478","volume":"462","author":"I Bartholom\u00e4us","year":"2009","unstructured":"Bartholom\u00e4us, I. et al. Effector T cell interactions with meningeal vascular structures in nascent autoimmune CNS lesions. Nature 462, 94\u201398 (2009).","journal-title":"Nature"},{"key":"1175_CR53","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1038\/nature16939","volume":"530","author":"C Schl\u00e4ger","year":"2016","unstructured":"Schl\u00e4ger, C. et al. Effector T-cell trafficking between the leptomeninges and the cerebrospinal fluid. Nature 530, 349\u2013353 (2016).","journal-title":"Nature"},{"key":"1175_CR54","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1038\/s41593-022-01108-3","volume":"25","author":"A Merlini","year":"2022","unstructured":"Merlini, A. et al. Distinct roles of the meningeal layers in CNS autoimmunity. Nat. Neurosci. 25, 887\u2013899 (2022).","journal-title":"Nat. Neurosci."},{"key":"1175_CR55","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-023-41580-4","volume":"14","author":"JA Mapunda","year":"2023","unstructured":"Mapunda, J. A. et al. VE-cadherin in arachnoid and pia mater cells serves as a suitable landmark for in vivo imaging of CNS immune surveillance and inflammation. Nat. Commun. 14, 5837 (2023).","journal-title":"Nat. Commun."},{"key":"1175_CR56","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1038\/nature25739","volume":"554","author":"M Vanlandewijck","year":"2018","unstructured":"Vanlandewijck, M. et al. A molecular atlas of cell types and zonation in the brain vasculature. Nature 554, 475\u2013480 (2018).","journal-title":"Nature"},{"key":"1175_CR57","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/0165-5728(94)90239-9","volume":"54","author":"JM Dopp","year":"1994","unstructured":"Dopp, J. M., Breneman, S. M. & Olschowka, J. A. Expression of ICAM-1, VCAM-1, L-selectin, and leukosialin in the mouse central nervous system during the induction and remission stages of experimental allergic encephalomyelitis. J. Neuroimmunol. 54, 129\u2013144 (1994).","journal-title":"J. Neuroimmunol."},{"key":"1175_CR58","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-023-42825-y","volume":"14","author":"NA Kearns","year":"2023","unstructured":"Kearns, N. A. et al. Dissecting the human leptomeninges at single-cell resolution. Nat. Commun. 14, 7036 (2023).","journal-title":"Nat. Commun."},{"key":"1175_CR59","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1016\/j.devcel.2020.09.020","volume":"55","author":"J Cui","year":"2020","unstructured":"Cui, J. et al. Inflammation of the embryonic choroid plexus barrier following maternal immune activation. Dev. Cell 55, 617\u2013628.e6 (2020).","journal-title":"Dev. Cell"},{"key":"1175_CR60","doi-asserted-by":"publisher","unstructured":"Verhaege, D. et al. Newly discovered base barrier cells provide compartmentalization of choroid plexus, brain and CSF. Preprint at bioRxiv https:\/\/doi.org\/10.1101\/2024.07.08.601696 (2024).","DOI":"10.1101\/2024.07.08.601696"},{"key":"1175_CR61","doi-asserted-by":"crossref","first-page":"eabf9277","DOI":"10.1126\/science.abf9277","volume":"373","author":"S Brioschi","year":"2021","unstructured":"Brioschi, S. et al. Heterogeneity of meningeal B cells reveals a lymphopoietic niche at the CNS borders. Science 373, eabf9277 (2021).","journal-title":"Science"},{"key":"1175_CR62","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1038\/s41593-018-0213-2","volume":"21","author":"F Herisson","year":"2018","unstructured":"Herisson, F. et al. Direct vascular channels connect skull bone marrow and the brain surface enabling myeloid cell migration. Nat. Neurosci. 21, 1209\u20131217 (2018).","journal-title":"Nat. Neurosci."},{"key":"1175_CR63","doi-asserted-by":"crossref","first-page":"2052","DOI":"10.1038\/s41593-023-01487-1","volume":"26","author":"JA Mazzitelli","year":"2023","unstructured":"Mazzitelli, J. A. et al. Skull bone marrow channels as immune gateways to the central nervous system. Nat. Neurosci. 26, 2052\u20132062 (2023).","journal-title":"Nat. Neurosci."},{"key":"1175_CR64","doi-asserted-by":"crossref","first-page":"2784","DOI":"10.1016\/j.immuni.2021.09.016","volume":"54","author":"Y Wang","year":"2021","unstructured":"Wang, Y. et al. Early developing B cells undergo negative selection by central nervous system-specific antigens in the meninges. Immunity 54, 2784\u20132794.e6 (2021).","journal-title":"Immunity"},{"key":"1175_CR65","doi-asserted-by":"crossref","first-page":"eabf7844","DOI":"10.1126\/science.abf7844","volume":"373","author":"A Cugurra","year":"2021","unstructured":"Cugurra, A. et al. Skull and vertebral bone marrow are myeloid cell reservoirs for the meninges and CNS parenchyma. Science 373, eabf7844 (2021).","journal-title":"Science"},{"key":"1175_CR66","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1038\/s41593-022-01029-1","volume":"25","author":"JA Mazzitelli","year":"2022","unstructured":"Mazzitelli, J. A. et al. Cerebrospinal fluid regulates skull bone marrow niches via direct access through dural channels. Nat. Neurosci. 25, 555\u2013560 (2022).","journal-title":"Nat. Neurosci."},{"key":"1175_CR67","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1038\/s41593-022-01060-2","volume":"25","author":"FE Pulous","year":"2022","unstructured":"Pulous, F. E. et al. Cerebrospinal fluid can exit into the skull bone marrow and instruct cranial hematopoiesis in mice with bacterial meningitis. Nat. Neurosci. 25, 567\u2013576 (2022).","journal-title":"Nat. Neurosci."},{"key":"1175_CR68","doi-asserted-by":"crossref","first-page":"2947","DOI":"10.1038\/s41591-024-03152-x","volume":"30","author":"C Dobersalske","year":"2024","unstructured":"Dobersalske, C. et al. Cranioencephalic functional lymphoid units in glioblastoma. Nat. Med. 30, 2947\u20132956 (2024).","journal-title":"Nat. Med."},{"key":"1175_CR69","doi-asserted-by":"crossref","first-page":"3706","DOI":"10.1016\/j.cell.2023.07.009","volume":"186","author":"ZI Kolabas","year":"2023","unstructured":"Kolabas, Z. I. et al. Distinct molecular profiles of skull bone marrow in health and neurological disorders. Cell 186, 3706\u20133725.e29 (2023).","journal-title":"Cell"},{"key":"1175_CR70","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1038\/s41586-024-07202-9","volume":"628","author":"Z Fitzpatrick","year":"2024","unstructured":"Fitzpatrick, Z. et al. Venous-plexus-associated lymphoid hubs support meningeal humoral immunity. Nature 628, 612\u2013619 (2024).","journal-title":"Nature"},{"key":"1175_CR71","doi-asserted-by":"crossref","first-page":"2103","DOI":"10.1016\/j.immuni.2022.10.005","volume":"55","author":"J Rebejac","year":"2022","unstructured":"Rebejac, J. et al. Meningeal macrophages protect against viral neuroinfection. Immunity 55, 2103\u20132117.e10 (2022).","journal-title":"Immunity"},{"key":"1175_CR72","doi-asserted-by":"crossref","first-page":"eadg6155","DOI":"10.1126\/sciimmunol.adg6155","volume":"8","author":"Y-C Kim","year":"2023","unstructured":"Kim, Y.-C. et al. Immaturity of immune cells around the dural venous sinuses contributes to viral meningoencephalitis in neonates. Sci. Immunol. 8, eadg6155 (2023).","journal-title":"Sci. Immunol."},{"key":"1175_CR73","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1038\/s41586-020-2886-4","volume":"587","author":"Z Fitzpatrick","year":"2020","unstructured":"Fitzpatrick, Z. et al. Gut-educated IgA plasma cells defend the meningeal venous sinuses. Nature 587, 472\u2013476 (2020).","journal-title":"Nature"},{"key":"1175_CR74","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1016\/j.it.2024.08.009","volume":"45","author":"NG Zanluqui","year":"2024","unstructured":"Zanluqui, N. G. & McGavern, D. B. Why do central nervous system barriers host a diverse immune landscape? Trends Immunol. 45, 738\u2013749 (2024).","journal-title":"Trends Immunol."},{"key":"1175_CR75","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1038\/s41586-024-07187-5","volume":"627","author":"H-G Lee","year":"2024","unstructured":"Lee, H.-G. et al. Disease-associated astrocyte epigenetic memory promotes CNS pathology. Nature 627, 865\u2013872 (2024).","journal-title":"Nature"},{"key":"1175_CR76","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1038\/s41586-018-0023-4","volume":"556","author":"A-C Wendeln","year":"2018","unstructured":"Wendeln, A.-C. et al. Innate immune memory in the brain shapes neurological disease hallmarks. Nature 556, 332\u2013338 (2018).","journal-title":"Nature"},{"key":"1175_CR77","doi-asserted-by":"crossref","first-page":"3745","DOI":"10.1016\/j.neuron.2023.09.002","volume":"111","author":"R Pietil\u00e4","year":"2023","unstructured":"Pietil\u00e4, R. et al. Molecular anatomy of adult mouse leptomeninges. Neuron 111, 3745\u20133764 (2023).","journal-title":"Neuron"},{"key":"1175_CR78","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1186\/s40478-022-01347-2","volume":"10","author":"LCD Smyth","year":"2022","unstructured":"Smyth, L. C. D. et al. Neutrophil\u2013vascular interactions drive myeloperoxidase accumulation in the brain in Alzheimer\u2019s disease. Acta Neuropathol. Commun. 10, 38 (2022).","journal-title":"Acta Neuropathol. Commun."},{"key":"1175_CR79","doi-asserted-by":"crossref","first-page":"2688","DOI":"10.1016\/j.immuni.2024.09.003","volume":"57","author":"JM Messmer","year":"2024","unstructured":"Messmer, J. M. et al. T lymphocyte recruitment to melanoma brain tumors depends on distinct venous vessels. Immunity 57, 2688\u20132703.e11 (2024).","journal-title":"Immunity"},{"key":"1175_CR80","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1016\/j.immuni.2015.11.010","volume":"43","author":"NB Pikor","year":"2015","unstructured":"Pikor, N. B. et al. Integration of Th17- and lymphotoxin-derived signals initiates meningeal-resident stromal cell remodeling to propagate neuroinflammation. Immunity 43, 1160\u20131173 (2015).","journal-title":"Immunity"},{"key":"1175_CR81","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pbio.3002389","volume":"21","author":"JF Quintana","year":"2023","unstructured":"Quintana, J. F. et al. The murine meninges acquire lymphoid tissue properties and harbour autoreactive B cells during chronic Trypanosoma brucei infection. PLoS Biol. 21, e3002389 (2023).","journal-title":"PLoS Biol."},{"key":"1175_CR82","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1093\/brain\/awm038","volume":"130","author":"R Magliozzi","year":"2007","unstructured":"Magliozzi, R. et al. Meningeal B-cell follicles in secondary progressive multiple sclerosis associate with early onset of disease and severe cortical pathology. Brain 130, 1089\u20131104 (2007).","journal-title":"Brain"},{"key":"1175_CR83","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1002\/ana.21379","volume":"65","author":"P Kivis\u00e4kk","year":"2009","unstructured":"Kivis\u00e4kk, P. et al. Localizing central nervous system immune surveillance: meningeal antigen-presenting cells activate T cells during experimental autoimmune encephalomyelitis. Ann. Neurol. 65, 457\u2013469 (2009).","journal-title":"Ann. Neurol."},{"key":"1175_CR84","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1038\/s41593-020-00770-9","volume":"24","author":"CE Dorrier","year":"2021","unstructured":"Dorrier, C. E. et al. CNS fibroblasts form a fibrotic scar in response to immune cell infiltration. Nat. Neurosci. 24, 234\u2013244 (2021).","journal-title":"Nat. Neurosci."},{"key":"1175_CR85","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.neuron.2018.08.030","volume":"100","author":"L Duan","year":"2018","unstructured":"Duan, L. et al. PDGFR\u03b2 cells rapidly relay inflammatory signal from the circulatory system to neurons via chemokine CCL2. Neuron 100, 183\u2013200.e8 (2018).","journal-title":"Neuron"},{"key":"1175_CR86","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1038\/s41586-020-03116-4","volume":"590","author":"LM Sanmarco","year":"2021","unstructured":"Sanmarco, L. M. et al. Gut-licensed IFN\u03b3+ NK cells drive LAMP1+TRAIL+ anti-inflammatory astrocytes. Nature 590, 473\u2013479 (2021).","journal-title":"Nature"},{"key":"1175_CR87","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-023-40982-8","volume":"14","author":"M Linnerbauer","year":"2023","unstructured":"Linnerbauer, M. et al. PD-L1 positive astrocytes attenuate inflammatory functions of PD-1 positive microglia in models of autoimmune neuroinflammation. Nat. Commun. 14, 5555 (2023).","journal-title":"Nat. Commun."},{"key":"1175_CR88","doi-asserted-by":"crossref","first-page":"1889","DOI":"10.4049\/jimmunol.162.4.1889","volume":"162","author":"C Choi","year":"1999","unstructured":"Choi, C. et al. Fas ligand and fas are expressed constitutively in human astrocytes and the expression increases with IL-1, IL-6, TNF-\u03b1, or IFN-\u03b3. J. Immunol. 162, 1889\u20131895 (1999).","journal-title":"J. Immunol."},{"key":"1175_CR89","doi-asserted-by":"crossref","first-page":"115344","DOI":"10.1016\/j.celrep.2025.115344","volume":"44","author":"P Hasel","year":"2025","unstructured":"Hasel, P. et al. Defining the molecular identity and morphology of glia limitans superficialis astrocytes in vertebrates. Cell Rep. 44, 115344 (2025).","journal-title":"Cell Rep."},{"key":"1175_CR90","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1038\/s41586-024-07283-6","volume":"628","author":"G Schevenels","year":"2024","unstructured":"Schevenels, G. et al. A brain-specific angiogenic mechanism enabled by tip cell specialization. Nature 628, 863\u2013871 (2024).","journal-title":"Nature"},{"key":"1175_CR91","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1038\/s41583-021-00454-8","volume":"22","author":"N MacAulay","year":"2021","unstructured":"MacAulay, N. Molecular mechanisms of brain water transport. Nat. Rev. Neurosci. 22, 326\u2013344 (2021).","journal-title":"Nat. Rev. Neurosci."},{"key":"1175_CR92","volume":"8","author":"Y Wang","year":"2019","unstructured":"Wang, Y. et al. Beta-catenin signaling regulates barrier-specific gene expression in circumventricular organ and ocular vasculatures. eLife 8, e43257 (2019).","journal-title":"eLife"},{"key":"1175_CR93","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1177\/15.3.160","volume":"15","author":"NH Becker","year":"1967","unstructured":"Becker, N. H., Novikoff, A. B. & Zimmerman, H. M. Fine structure observations of the uptake of intravenously injected peroxidase by the rat choroid plexus. J. Histochem. Cytochem. 15, 160\u2013165 (1967).","journal-title":"J. Histochem. Cytochem."},{"key":"1175_CR94","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-022-31257-9","volume":"13","author":"H Mestre","year":"2022","unstructured":"Mestre, H. et al. Periarteriolar spaces modulate cerebrospinal fluid transport into brain and demonstrate altered morphology in aging and Alzheimer\u2019s disease. Nat. Commun. 13, 3897 (2022).","journal-title":"Nat. Commun."},{"key":"1175_CR95","doi-asserted-by":"publisher","unstructured":"Ewing-Crystal, N. A. et al. Dynamic fibroblast-immune interactions shape wound healing after brain injury. Preprint at bioRxiv https:\/\/doi.org\/10.1101\/2024.03.13.584873 (2024).","DOI":"10.1101\/2024.03.13.584873"},{"key":"1175_CR96","volume":"15","author":"X Xue","year":"2024","unstructured":"Xue, X. et al. Heterogeneous fibroblasts contribute to fibrotic scar formation after spinal cord injury in mice and monkeys. Nat. Commun. 15, 6321 (2024).","journal-title":"Nat. Commun."},{"key":"1175_CR97","doi-asserted-by":"crossref","first-page":"1507","DOI":"10.1016\/j.ccell.2024.08.012","volume":"42","author":"SS Watson","year":"2024","unstructured":"Watson, S. S. et al. Fibrotic response to anti-CSF-1R therapy potentiates glioblastoma recurrence. Cancer Cell 42, 1507\u20131527.e11 (2024).","journal-title":"Cancer Cell"},{"key":"1175_CR98","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1038\/s41586-021-04369-3","volume":"603","author":"AC Yang","year":"2022","unstructured":"Yang, A. C. et al. A human brain vascular atlas reveals diverse mediators of Alzheimer\u2019s risk. Nature 603, 885\u2013892 (2022).","journal-title":"Nature"},{"key":"1175_CR99","volume":"12","author":"J Wang","year":"2023","unstructured":"Wang, J., Rattner, A. & Nathans, J. Bacterial meningitis in the early postnatal mouse studied at single-cell resolution. eLife 12, e86130 (2023).","journal-title":"eLife"},{"key":"1175_CR100","doi-asserted-by":"crossref","first-page":"16","DOI":"10.3389\/fnins.2015.00016","volume":"9","author":"S Whish","year":"2015","unstructured":"Whish, S. et al. The inner CSF\u2013brain barrier: developmentally controlled access to the brain via intercellular junctions. Front. Neurosci. 9, 16 (2015).","journal-title":"Front. Neurosci."}],"container-title":["Nature Reviews Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41577-025-01175-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41577-025-01175-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41577-025-01175-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T12:04:12Z","timestamp":1758888252000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41577-025-01175-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,2]]},"references-count":100,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2025,10]]}},"alternative-id":["1175"],"URL":"https:\/\/doi.org\/10.1038\/s41577-025-01175-0","relation":{},"ISSN":["1474-1733","1474-1741"],"issn-type":[{"value":"1474-1733","type":"print"},{"value":"1474-1741","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,2]]},"assertion":[{"value":"2 April 2025","order":1,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 May 2025","order":2,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}