0000000000676810
AUTHOR
Sebastian Richers
Cross-recognition of a myelin peptide by CD8+ T cells in the CNS is not sufficient to promote neuronal damage.
Multiple sclerosis (MS) is an inflammatory disease of the CNS thought to be driven by CNS-specific T lymphocytes. Although CD8+T cells are frequently found in multiple sclerosis lesions, their distinct role remains controversial because direct signs of cytotoxicity have not been confirmedin vivo. In the present work, we determined that murine ovalbumin-transgenic (OT-1) CD8+T cells recognize the myelin peptide myelin oligodendrocyte glycoprotein 40–54 (MOG40–54) bothin vitroandin vivo. The aim of this study was to investigate whether such cross-recognizing CD8+T cells are capable of inducing CNS damagein vivo. Using intravital two-photon microscopy in the mouse model of multiple sclerosis, …
Molecular cause and functional impact of altered synaptic lipid signaling due to a prg‐1 gene SNP
Loss of plasticity-related gene 1 (PRG-1), which regulates synaptic phospholipid signaling, leads to hyperexcitability via increased glutamate release altering excitation/inhibition (E/I) balance in cortical networks. A recently reported SNP in prg-1 (R345T/ mutPRG-1) affects ~5 million European and US citizens in a monoallelic variant. Our studies show that this mutation leads to a loss-of-PRG-1 function at the synapse due to its inability to control lysophosphatidic acid (LPA) levels via a cellular uptake mechanism which appears to depend on proper glycosylation altered by this SNP. PRG-1 +/ mice, which are animal correlates of human PRG-1 +/mut carriers, showed an altered cortical networ…