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

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.