The pathogenesis of neuropsychiatric lupus (NPSLE) is believed to include the entry of circulating neuropathic antibodies to the brain via a pathologically permeable blood-brain barrier (BBB). Surprisingly, we found that BBB permeability is normal in the NPSLE mouse model. Here we show that abnormal function of the blood-cerebrospinal fluid barrier (BCSFB) in the choroid plexus (CP) underlies brain exposure to neuropathic antibodies. NPSLE CP exhibits unique and robust immune cells barrier-crossing into the CSF. The crossing does not involve mere epithelial tissue destruction but rather a controlled trans-epithelial migration process. In addition, we find extensive evidence for an inflammatory process within CP parenchyma, of both the mouse model and in NPSLE patients, that includes the formation of Tertiary Lymphoid Structures. Finally, we present new approaches to investigate this neuro-auto-immune hub, highlighting the role of CP epithelium, CP vasculature, and immune cells. These include new imaging technics and unique transcriptome profiling approaches. Lessons from neuropsychiatric lupus might pave the road to developing multidimensional opportunities for therapeutic interventions, relevant to CNS autoimmunity and to neuro-immunity in general.