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dc.contributor.authorRobert, Stephanie M
dc.contributor.authorReeves, Benjamin C
dc.contributor.authorKiziltug, Emre
dc.contributor.authorDuy, Phan Q
dc.contributor.authorKarimy, Jason K
dc.contributor.authorMansuri, M Shahid
dc.contributor.authorMarlier, Arnaud
dc.contributor.authorAllington, Garrett
dc.contributor.authorGreenberg, Ana B W
dc.contributor.authorDeSpenza, Tyrone
dc.contributor.authorSingh, Amrita K
dc.contributor.authorZeng, Xue
dc.contributor.authorMekbib, Kedous Y
dc.contributor.authorKundishora, Adam J
dc.contributor.authorNelson-Williams, Carol
dc.contributor.authorHao, Le Thi
dc.contributor.authorZhang, Jinwei
dc.contributor.authorLam, TuKiet T
dc.contributor.authorWilson, Rashaun
dc.contributor.authorButler, William E
dc.contributor.authorDiluna, Michael L
dc.contributor.authorFeinberg, Philip A
dc.contributor.authorSchafer, Dorothy P
dc.contributor.authorMovahedi, Kiavash
dc.contributor.authorTannenbaum, Allen
dc.contributor.authorKoundal, Sunil
dc.contributor.authorChen, Xinan
dc.contributor.authorBenveniste, Helene
dc.contributor.authorLimbrick, David D
dc.contributor.authorSchiff, Steven J
dc.contributor.authorCarter, Bob S
dc.contributor.authorGunel, Murat
dc.contributor.authorSimard, J Marc
dc.contributor.authorLifton, Richard P
dc.contributor.authorAlper, Seth L
dc.contributor.authorDelpire, Eric
dc.contributor.authorKahle, Kristopher T
dc.date.accessioned2023-03-20T15:27:20Z
dc.date.available2023-03-20T15:27:20Z
dc.date.issued2023-02-16
dc.identifier.citationRobert SM, Reeves BC, Kiziltug E, Duy PQ, Karimy JK, Mansuri MS, Marlier A, Allington G, Greenberg ABW, DeSpenza T Jr, Singh AK, Zeng X, Mekbib KY, Kundishora AJ, Nelson-Williams C, Hao LT, Zhang J, Lam TT, Wilson R, Butler WE, Diluna ML, Feinberg P, Schafer DP, Movahedi K, Tannenbaum A, Koundal S, Chen X, Benveniste H, Limbrick DD Jr, Schiff SJ, Carter BS, Gunel M, Simard JM, Lifton RP, Alper SL, Delpire E, Kahle KT. The choroid plexus links innate immunity to CSF dysregulation in hydrocephalus. Cell. 2023 Feb 16;186(4):764-785.e21. doi: 10.1016/j.cell.2023.01.017. PMID: 36803604.en_US
dc.identifier.eissn1097-4172
dc.identifier.doi10.1016/j.cell.2023.01.017en_US
dc.identifier.pmid36803604
dc.identifier.urihttp://hdl.handle.net/20.500.14038/51862
dc.description.abstractThe choroid plexus (ChP) is the blood-cerebrospinal fluid (CSF) barrier and the primary source of CSF. Acquired hydrocephalus, caused by brain infection or hemorrhage, lacks drug treatments due to obscure pathobiology. Our integrated, multi-omic investigation of post-infectious hydrocephalus (PIH) and post-hemorrhagic hydrocephalus (PHH) models revealed that lipopolysaccharide and blood breakdown products trigger highly similar TLR4-dependent immune responses at the ChP-CSF interface. The resulting CSF "cytokine storm", elicited from peripherally derived and border-associated ChP macrophages, causes increased CSF production from ChP epithelial cells via phospho-activation of the TNF-receptor-associated kinase SPAK, which serves as a regulatory scaffold of a multi-ion transporter protein complex. Genetic or pharmacological immunomodulation prevents PIH and PHH by antagonizing SPAK-dependent CSF hypersecretion. These results reveal the ChP as a dynamic, cellularly heterogeneous tissue with highly regulated immune-secretory capacity, expand our understanding of ChP immune-epithelial cell cross talk, and reframe PIH and PHH as related neuroimmune disorders vulnerable to small molecule pharmacotherapy.en_US
dc.language.isoenen_US
dc.relation.ispartofCellen_US
dc.relation.urlhttps://doi.org/10.1016/j.cell.2023.01.017en_US
dc.rightsCopyright © 2023 Elsevier Inc. All rights reserved.en_US
dc.subjectCSFen_US
dc.subjectNKCC1en_US
dc.subjectSPAKen_US
dc.subjectblood-CSF barrieren_US
dc.subjectcerebrospinal fluiden_US
dc.subjectchoroid plexusen_US
dc.subjecthydrocephalusen_US
dc.subjectneuro-inflammationen_US
dc.titleThe choroid plexus links innate immunity to CSF dysregulation in hydrocephalusen_US
dc.typeJournal Articleen_US
dc.source.journaltitleCell
dc.source.volume186
dc.source.issue4
dc.source.beginpage764
dc.source.endpage785.e21
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.identifier.journalCell
dc.contributor.departmentBrudnick Neuropsychiatric Research Instituteen_US
dc.contributor.departmentMorningside Graduate School of Biomedical Sciencesen_US
dc.contributor.departmentNeurobiologyen_US
dc.contributor.departmentSchafer Lab
dc.contributor.studentPhilip Feinberg
dc.description.thesisprogramMD/PhD


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