Biology subjects

van Olst, L.

Publications and source records attributed to van Olst, L..

2 recordsLinked to original sources

bioRxiv2021

Single-cell profiling reveals periventricular CD56bright NK cell accumulation in multiple sclerosis

Multiple sclerosis (MS) is a chronic demyelinating disease characterised by immune cell infiltration resulting in lesions that preferentially affect periventricular areas of the brain. Despite research efforts to define the role of various immune cells in MS pathogenesis, the focus has been on a few immune cell populations while full-spectrum analysis, encompassing others such as natural killer (NK) cells, has not been performed. Here, we used single-cell mass cytometry (CyTOF) to profile the immune landscape of brain periventricular areas - septum and choroid plexus - and blood from MS donors and controls with and without other neurological diseases. Using a 37-marker panel, we revealed the infiltration of T cells and antibody-secreting cells in periventricular brain regions and identified a novel NK cell signature specific to MS. CD56bright NK cells accumulated in the septum of MS donors, displaying an activated and migratory phenotype that was similar to that of CD56bright NK cells in their circulation. We validated this signature by multiplex immunohistochemistry and found that NK cells with high expression of granzyme K, which is typical of the CD56bright subset, accumulated in both periventricular lesions and the choroid plexus. Together, our multi-tissue single-cell data suggests that CD56bright NK cells infiltrate the periventricular brain regions in MS patients via both the blood-brain and blood-CSF barriers and brings NK cells to the spotlight of MS pathology.

immunology↗

bioRxiv2020

Meningeal inflammation in multiple sclerosis induces phenotypic changes in cortical microglia that differentially associate with neurodegeneration

Meningeal inflammation strongly associates with demyelination and neuronal loss in the underlying cortex of progressive MS patients, contributing to clinical disability. However, the pathological mechanisms of meningeal inflammation-induced cortical pathology are still largely elusive. Using extensive analysis of human post-mortem tissue, we identified two distinct microglial phenotypes, termed MS1 and MS2, in the cortex of progressive MS patients. These phenotypes differed in morphology and protein expression, but both associated with inflammation of the overlying meninges. We could replicate the MS-specific microglial phenotypes in a novel in vivo rat model for progressive MS-like meningeal inflammation, with microglia present at 1 month post-induction resembling MS1 microglia whereas those at 2 months acquired an MS2-like phenotype. Interestingly, MS1 microglia were involved in presynaptic displacement and phagocytosis and associated with a relative sparing of neurons in the MS and animal cortex. In contrast, the presence of MS2 microglia coincided with substantial neuronal loss. Taken together, we uncovered that in response to meningeal inflammation, microglia acquire two distinct phenotypes that differentially associate with neurodegeneration in the progressive MS cortex. Our data suggests that these phenotypes occur sequentially and that microglia may lose their protective properties over time, contributing to neuronal loss.

neuroscience↗