Stroke induces disease-specific myeloid cells in the brain parenchyma and pia
We deeply characterize tissue-resident leukocytes in meninges and brain parenchyma and discover that leukocytes respond differently to stroke depending on their site of residence. We thereby discover a unique phenotype of myeloid cells exclusive to the brain after stroke. These stroke-associated myeloid cells partially resemble neurodegenerative disease-associated microglia. They are mainly of resident microglial origin, partially conserved in humans and exhibit a lipid-phagocytosing phenotype. Blocking markers specific for these cells partially ameliorates stroke outcome thus providing a potential therapeutic target.
Feb 1, 2022
Bcl6 controls meningeal Th17-B cell interaction in murine neuroinflammation.
By generating a compartment-specific transcriptional map of meningeal versus parenchymal leukocytes in experimental neuroinflammation, we found a follicular phenotype of meningeal B cells and a corresponding follicular helper-like phenotype in meningeal Th17 cells. The meninges thus instructed a site-specific local phenotype to proinflammatory autoreactive T cells. We identified the transcription factor Bcl6 in Th17 cells to promote interactions with meningeal B cells, isotype-switching, and B cell-supporting chemokines. This may describe a mechanism controlling meningeal autoimmunity and helps understanding how the meninges, as a recently recognized immunologically active site, contribute to autoimmune tissue damage in multiple sclerosis.
Sep 1, 2021
Cerebrospinal fluid flow cytometry distinguishes psychosis spectrum disorders from differential diagnoses
We performed basic CSF analysis and multi-dimensional flow cytometry of CSF and blood cells from 59 patients with primary psychotic disorders in comparison to inflammatory and non-inflammatory controls. We found an expansion of monocytes in the blood and CSF of psychosis patients. A machine learning model incorporating blood and CSF parameters differentated psychosis from non-inflammatory controls better than individual paramaters.
Aug 1, 2021
Single-cell profiling of CNS border compartment leukocytes reveals that B cells and their progenitors reside in non-diseased meninges.
Based on single-cell transcriptomics, we here identify a highly location-specific composition and expression profile of tissue-resident leukocytes in CNS border compartments featuring B cells and their progenitors in the dura as an unexpected site of B cell residence.
Jul 1, 2021
Leukocyte profiles in blood and CSF distinguish neurosarcoidosis from multiple sclerosis
Apr 1, 2020
Integrated single cell analysis of blood and cerebrospinal fluid leukocytes in multiple sclerosis
Jan 1, 2020