NEFL and systemic lupus erythematosus: The mechanisms linking systemic autoimmunity to neuronal injury and neuropsychiatric symptoms remain poorly understood.<h4>Methods</h4>Using the lupus-prone MRL/Lpr mouse model, we integrated systemic cytokine profiling, plasma neurofilament light chain (NfL), region-specific CNS cytokine mRNA mapping, cortical metabolomics, and behavioral analyses to dissect immune-metabolic-neuronal interactions.<h4>Results</h4>Inflammation was dominated by a Th1 cytokine program, with interferon-gamma emerging as a prominent component of the inflammatory profile.