IRF7 in peripheral monocytes drives BBB disruption in anti-NMDAR encephalitis

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a severe neurological disorder characterized by the presence of autoantibodies against the NMDAR and blood-brain barrier (BBB) disruption. This study investigates the involvement of monocytes and interferon regulatory factor 7 (IRF7) in BBB leakage of this disease. In anti-NMDAR encephalitis patients, the circulating monocytes count was positively correlated with BBB disruption, besides, IRF7 was activated in these cells. In peripheral blood and brain of our anti-NMDAR encephalitis mouse model, increased monocytes and elevated IRF7 expression within these cells were found. Additionally, in the blood and brain of this model, the quantity of monocytes and their IRF7 expression level were positively correlated with behavioral deficits. IRF7-KO mice were subjected to anti-NMDAR encephalitis modeling and exhibited milder disease severity and reduced BBB disruption compared to their WT counterparts. Bone marrow derived macrophages (BMDMs) from IRF7-KO mice showed diminished capacity to disrupt BBB compared with BMDMs from WT mice in in vitro study. Our findings suggest that IRF7 plays a critical role in the pathogenesis of anti-NMDAR encephalitis by modulating monocyte's capacity to disrupt BBB. Targeting IRF7 may offer a novel therapeutic strategy for this devastating neurological condition.