The choroid plexus is a key cerebral invasion route for T cells after stroke

  • Gemma Llovera
  • Corinne Benakis
  • Gaby Enzmann
  • Ruiyao Cai
  • Thomas Arzberger
  • Alireza Ghasemigharagoz
  • Xiang Mao
  • Rainer Malik
  • Ivana Lazarevic
  • Sabine Liebscher
  • Ali Ertürk
  • Lilja Meissner
  • Denis Vivien
  • Christof Haffner
  • Nikolaus Plesnila
  • Joan Montaner
  • Britta Engelhardt
  • Arthur Liesz
Original Paper

Abstract

Neuroinflammation contributes substantially to stroke pathophysiology. Cerebral invasion of peripheral leukocytes—particularly T cells—has been shown to be a key event promoting inflammatory tissue damage after stroke. While previous research has focused on the vascular invasion of T cells into the ischemic brain, the choroid plexus (ChP) as an alternative cerebral T-cell invasion route after stroke has not been investigated. We here report specific accumulation of T cells in the peri-infarct cortex and detection of T cells as the predominant population in the ipsilateral ChP in mice as well as in human post-stroke autopsy samples. T-cell migration from the ChP to the peri-infarct cortex was confirmed by in vivo cell tracking of photoactivated T cells. In turn, significantly less T cells invaded the ischemic brain after photothrombotic lesion of the ipsilateral ChP and in a stroke model encompassing ChP ischemia. We detected a gradient of CCR2 ligands as the potential driving force and characterized the neuroanatomical pathway for the intracerebral migration. In summary, our study demonstrates that the ChP is a key invasion route for post-stroke cerebral T-cell invasion and describes a CCR2-ligand gradient between cortex and ChP as the potential driving mechanism for this invasion route.

Supplementary material

401_2017_1758_MOESM1_ESM.pdf (616 kb)
Supplementary material 1 (PDF 615 kb)

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Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  • Gemma Llovera
    • 1
    • 2
  • Corinne Benakis
    • 1
  • Gaby Enzmann
    • 3
  • Ruiyao Cai
    • 1
    • 2
  • Thomas Arzberger
    • 4
    • 5
  • Alireza Ghasemigharagoz
    • 1
  • Xiang Mao
    • 1
  • Rainer Malik
    • 1
  • Ivana Lazarevic
    • 3
  • Sabine Liebscher
    • 2
    • 6
  • Ali Ertürk
    • 1
    • 2
  • Lilja Meissner
    • 1
  • Denis Vivien
    • 7
  • Christof Haffner
    • 1
  • Nikolaus Plesnila
    • 1
    • 2
  • Joan Montaner
    • 8
  • Britta Engelhardt
    • 3
  • Arthur Liesz
    • 1
    • 2
  1. 1.Institute for Stroke and Dementia ResearchKlinikum der Universität MünchenMunichGermany
  2. 2.Munich Cluster for Systems Neurology (SyNergy)MunichGermany
  3. 3.Theodor Kocher InstituteUniversity of BernBernSwitzerland
  4. 4.Center for Neuropathology and Prion ResearchLudwig-Maximilians-UniversitätMunichGermany
  5. 5.Department of Psychiatry and PsychotherapyLudwig-Maximilians-UniversitätMunichGermany
  6. 6.Institute of Clinical Neuroimmunology, Klinikum der Universität MünchenLudwig-Maximilians-UniversityMunichGermany
  7. 7.INSERM, UMR-S U919, Institut National de la Santé Et de la Recherche Médicale (INSERM), Team Serine Proteases and Pathophysiology of the Neurovascular Unit, GIP CYCERONUniversity Caen Basse-NormandieCaen CedexFrance
  8. 8.Neurovascular Research Laboratory, Vall d’Hebron Research Institute (VHIR)Universitat Autònoma de BarcelonaBarcelonaSpain

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