{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T12:22:56Z","timestamp":1787574176286,"version":"build-2736575974"},"reference-count":136,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:00:00Z","timestamp":1787529600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>The central nervous system has long been considered an immune-privileged organ, but discoveries about meningeal lymphatics, meningeal immune cells, cerebrospinal fluid (CSF)-interstitial fluid (ISF) exchange, and aquaporin-4 (AQP4)-associated glymphatic-like transport are reshaping our understanding of waste clearance and immune surveillance in the brain. However, there are obvious breaks in the current model system. Animal models possess complete circulatory and meningeal structures, but are limited by species differences, imaging depth, operability, and high throughput. Traditional two-dimensional (2D) culture and transwell models lack 3D brain parenchymal structure, low-speed fluid dynamics, and the meningeal immune microenvironment. This paper proposes the concept of \u201cbrain parenchyma-lymphoid-meningeal immune assembly chip\u201d, which integrates brain organoids containing neurons, astrocytes and microglia, CSF-like fluid derived from choroid plexus organoids, microfluidic lymphatic channels, and meningeal immune modules containing meningeal lymphatic endothelium, meningeal fibroblasts, macrophages, and dendritic cells. Currently, the various component technologies required for this platform are still at different stages of experimental maturity and have not yet been integrated into a single system. This review discusses existing issues such as the cellular composition of the brain parenchyma module, the engineering simulation of glymphatic dynamics, the reconstruction of the meningeal lymphatic and immune interface, disease applications, and validation standards. It also outlines a phased development roadmap to build a platform capable of tracking the continuous process of \u201cpathological product generation-fluid clearance-meningeal immune sensing-inflammatory feedback\u201d under simulated human brain conditions, providing new tools for mechanism analysis and drug screening in neurodegenerative diseases, brain injury, and neuro-immunological diseases.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1931370","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T11:33:26Z","timestamp":1787571206000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrating brain organoids, meningeal immunity, and glymphatic dynamics: toward modeling neuroimmune clearance and crosstalk in disease"],"prefix":"10.3389","volume":"17","author":[{"given":"Xiaolei","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Cancer Center, Army Medical Center of PLA (Daping Hospital), Army Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Neurology and State Key Laboratory of Biotherapy, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Cancer Center, Army Medical Center of PLA (Daping Hospital), Army Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruyi","family":"Hang","sequence":"additional","affiliation":[{"name":"Department of Cancer Center, Army Medical Center of PLA (Daping Hospital), Army Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ce","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Cancer Center, Army Medical Center of PLA (Daping Hospital), Army Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengxia","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Cancer Center, Army Medical Center of PLA (Daping Hospital), Army Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/nature14432","article-title":"Structural and functional features of central nervous system lymphatic vessels","volume":"523","author":"Louveau","year":"2015","journal-title":"Nature"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20142290","article-title":"A 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