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The immune-regulatory functions of neurons are largely unknown despite the growing evidence showing the presence of immune cells in the central nervous system (CNS). This project aims to characterize a novel neuroimmune interaction, whereby neurons activate natural killer T (NKT) cells in a CD1d-dependent manner. Interestingly, neurons expressing CD1d appear to localize near neuroimmune niches in the CNS and counteract neuropathology, emphasizing the project’s potential translational impact.