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The choroid plexus links innate immunity to CSF dysregulation in hydrocephalus.
Robert, Stephanie M; Reeves, Benjamin C; Kiziltug, Emre; Duy, Phan Q; Karimy, Jason K; Mansuri, M Shahid; Marlier, Arnaud; Allington, Garrett; Greenberg, Ana B W; DeSpenza, Tyrone; Singh, Amrita K; Zeng, Xue; Mekbib, Kedous Y; Kundishora, Adam J; Nelson-Williams, Carol; Hao, Le Thi; Zhang, Jinwei; Lam, TuKiet T; Wilson, Rashaun; Butler, William E; Diluna, Michael L; Feinberg, Philip; Schafer, Dorothy P; Movahedi, Kiavash; Tannenbaum, Allen; Koundal, Sunil; Chen, Xinan; Benveniste, Helene; Limbrick, David D; Schiff, Steven J; Carter, Bob S; Gunel, Murat; Simard, J Marc; Lifton, Richard P; Alper, Seth L; Delpire, Eric; Kahle, Kristopher T.
Afiliação
  • Robert SM; Department of Neurosurgery, Yale School of Medicine, New Haven, CT 06520, USA.
  • Reeves BC; Department of Neurosurgery, Yale School of Medicine, New Haven, CT 06520, USA.
  • Kiziltug E; Department of Neurosurgery, Yale School of Medicine, New Haven, CT 06520, USA.
  • Duy PQ; Department of Neurosurgery, Yale School of Medicine, New Haven, CT 06520, USA.
  • Karimy JK; Department of Neurosurgery, Yale School of Medicine, New Haven, CT 06520, USA.
  • Mansuri MS; Department of Neurosurgery, Yale School of Medicine, New Haven, CT 06520, USA; Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT 06520, USA.
  • Marlier A; Department of Neurosurgery, Yale School of Medicine, New Haven, CT 06520, USA.
  • Allington G; Department of Neurosurgery, Yale School of Medicine, New Haven, CT 06520, USA; Department of Pathology, Yale School of Medicine, New Haven, CT 06520, USA.
  • Greenberg ABW; Department of Neurosurgery, Yale School of Medicine, New Haven, CT 06520, USA.
  • DeSpenza T; Department of Neurosurgery, Yale School of Medicine, New Haven, CT 06520, USA.
  • Singh AK; Department of Neurosurgery, Yale School of Medicine, New Haven, CT 06520, USA.
  • Zeng X; Department of Neurosurgery, Yale School of Medicine, New Haven, CT 06520, USA.
  • Mekbib KY; Department of Neurosurgery, Yale School of Medicine, New Haven, CT 06520, USA.
  • Kundishora AJ; Department of Neurosurgery, Yale School of Medicine, New Haven, CT 06520, USA.
  • Nelson-Williams C; Department of Neurosurgery, Yale School of Medicine, New Haven, CT 06520, USA.
  • Hao LT; Department of Neurosurgery, Yale School of Medicine, New Haven, CT 06520, USA.
  • Zhang J; Institute of Biomedical and Clinical Sciences, University of Exeter Medical School, Hatherly Laboratory, Exeter EX1 2LU, UK.
  • Lam TT; Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT 06520, USA; Keck MS & Proteomics Resource, Yale University School of Medicine, New Haven, CT 06520, USA.
  • Wilson R; Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT 06520, USA; Keck MS & Proteomics Resource, Yale University School of Medicine, New Haven, CT 06520, USA.
  • Butler WE; Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
  • Diluna ML; Department of Neurosurgery, Yale School of Medicine, New Haven, CT 06520, USA.
  • Feinberg P; Department of Neurobiology, Brudnick Neuropsychiatric Research Institute University of Massachusetts Chan Medical School, Worcester, MA 01655, USA; Medical Scientist Training Program, UMass Chan Medical School, Worcester, MA 01655, USA.
  • Schafer DP; Department of Neurobiology, Brudnick Neuropsychiatric Research Institute University of Massachusetts Chan Medical School, Worcester, MA 01655, USA.
  • Movahedi K; Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, 1050 Brussels, Belgium; Myeloid Cell Immunology Laboratory, VIB Center for Inflammation Research, 1050 Brussels, Belgium.
  • Tannenbaum A; Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, NY 11794, USA; Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York City, NY 11794, USA.
  • Koundal S; Department of Anesthesiology, Yale School of Medicine, New Haven, CT 06520, USA.
  • Chen X; Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, NY 11794, USA.
  • Benveniste H; Department of Anesthesiology, Yale School of Medicine, New Haven, CT 06520, USA.
  • Limbrick DD; Department of Neurosurgery, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • Schiff SJ; Department of Neurosurgery, Yale School of Medicine, New Haven, CT 06520, USA.
  • Carter BS; Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
  • Gunel M; Department of Neurosurgery, Yale School of Medicine, New Haven, CT 06520, USA.
  • Simard JM; Department of Neurosurgery, University of Maryland, School of Medicine, Baltimore, MD 21201, USA; Department of Pathology, University of Maryland, School of Medicine, Baltimore, MD 21201, USA; Department of Physiology, University of Maryland, School of Medicine, Baltimore, MD 21201, USA.
  • Lifton RP; Laboratory of Human Genetics and Genomics, the Rockefeller University, New York, NY 10065, USA.
  • Alper SL; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
  • Delpire E; Department of Anesthesiology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
  • Kahle KT; Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Broad Institute of Harvard and MIT, Cambridge, MA, 02142, USA; Department of Neurosurgery and Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA. Electronic addre
Cell ; 186(4): 764-785.e21, 2023 02 16.
Article em En | MEDLINE | ID: mdl-36803604
ABSTRACT
The 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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Plexo Corióideo / Hidrocefalia Limite: Humans Idioma: En Revista: Cell Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Plexo Corióideo / Hidrocefalia Limite: Humans Idioma: En Revista: Cell Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos