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The choroid plexus synergizes with immune cells during neuroinflammation

Affiliations
  • 1Department of Pathology, Boston Children’s Hospital and Harvard Medical School, Boston, MA 02115, USA.
  • 2Division of Gastroenterology, Hepatology, and Nutrition, Boston Children’s Hospital, Boston, MA 02115, USA; Graduate Program in Biological and Biomedical Sciences, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • 3Department of Pathology, Boston Children’s Hospital and Harvard Medical School, Boston, MA 02115, USA; Graduate Program in Biophysics, Harvard University, Cambridge, MA 02138, USA.
  • 4Department of Pathology, Boston Children’s Hospital and Harvard Medical School, Boston, MA 02115, USA; Graduate Program in Biological and Biomedical Sciences, Harvard Medical School, Boston, MA 02115, USA; Harvard MD-PhD Program, Harvard Medical School, Boston, MA 02115, USA.
  • 5Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.
  • 6Department of Pathology, Boston Children’s Hospital and Harvard Medical School, Boston, MA 02115, USA; Harvard College, Harvard University, Cambridge, MA 02138, USA.
  • 7Harvard MD-PhD Program, Harvard Medical School, Boston, MA 02115, USA; Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA; Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.

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August 1, 2024

Abstract

The choroid plexus (ChP) is a vital brain barrier and source of cerebrospinal fluid (CSF). Here, we use longitudinal two-photon imaging in awake mice and single-cell transcriptomics to elucidate the mechanisms of ChP regulation of brain inflammation. We used intracerebroventricular injections of lipopolysaccharides (LPS) to model meningitis in mice and observed that neutrophils and monocytes accumulated in the ChP stroma and surged across the epithelial barrier into the CSF. Bi-directional recruitment of monocytes from the periphery and, unexpectedly, macrophages from the CSF to the ChP helped eliminate neutrophils and repair the barrier. Transcriptomic analyses detailed the molecular steps accompanying this process and revealed that ChP epithelial cells transiently specialize to nurture immune cells, coordinating their recruitment, survival, and differentiation as well as regulation of the tight junctions that control the permeability of the ChP brain barrier. Collectively, we provide a mechanistic understanding and a comprehensive roadmap of neuroinflammation at the ChP brain barrier.

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