摘要：SummaryNeurodegeneration is a process involving both cell autonomous and non-cell autonomous neuron loss, followed by a collapse of neural networks, but its pathogenesis is poorly understood. We have previously demonstrated that Eomes-positive helper T (Eomes + Th) cells recognizing LINE-1(L1)-derived prototypic antigen ORF1 mediate neurotoxicity associated with the neurodegenerative pathology of experimental autoimmune encephalomyelitis (EAE). Here, we show that Eomes + Th cells accumulate in the CNS of mouse models of authentic neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and Alzheimer’s disease (AD), and secrete the neurotoxic granzyme B after encounter with ORF1 antigen. Multimodal derepression of neuronal L1 transcription is observed in EAE and ALS/AD models during neurodegeneration in active and cell cycle-mediated manner, respectively. These data suggest that the adventitious concurrence of immune-mediated neurodegenerative traits by Eomes + Th cells and ectopic expression of L1-derived antigen(s) in the inflamed CNS may materialize a communal and previously unappreciated pathogenesis of neurodegeneration.Graphical abstractDisplay OmittedHighlights•Eomes + Th cells accumulate in the CNS with undergoing neurodegeneration in common•Multimodal L1 derepression is emerged in neuron cells under neurodegeneration•Eomes + Th cells recognize L1-ORF1 antigen to exert neurotoxicity via granzyme B•Immune-mediated neurotoxicity may embody a novel pathogenesis of neurodegenerationBiological sciences; Neuroscience; Immunology
