Neuron-Specific Vitamin D Signaling Attenuates Microglia Activation and CNS Autoimmunity

摘要: Low vitamin D during childhood is associated with an increased risk of developing multiple sclerosis (MS) as adult. Given that has anti-inflammatory properties, it been postulated the relationship between MS and low due to immune dysregulation. Since receptor (VDR) expressed in many cell types, this study investigated alternative hypothesis - neuron-specific VDR signaling induces molecules protect central nervous system from autoimmunity. Using media neurons treated calcitriol, active form D3, LPS-activated microglia had a reduction pro-inflammatory molecules, reciprocal induction molecules. IL-34 critical homeostasis microglia, was previously shown be induced endothelial cells by D, we potential molecule D. Treatment reduced cytokine production enhanced expression transcripts. However, neutralizing neuronal conditioned only impacted IL-6 not broader phenotype microglia. To mimic children, used inducible mouse model which partially deleted juvenile mice. Partial deletion early life resulted exacerbated CNS autoimmunity adult Overall, illustrated promotes state may enhance