Neuronal NR4A1 deficiency drives complement-coordinated synaptic stripping by microglia in a mouse model of lupus.

ABSTRACT: Neuropsychiatric lupus (NPSLE) is a frequent manifestation of systemic lupus erythematosus (SLE) that occurs in 40-90% of SLE patients; however, the underlying mechanisms remain elusive, causing a severe lack of therapeutic targets for this condition. Here, we show that complement-coordinated elimination of synapses participated in NPSLE in MRL/lpr mice, a lupus-prone murine model. We demonstrated that lupus mice developed increased anxiety-like behaviors and persistent phagocytic microglial reactivation before overt peripheral lupus pathology. In the lupus brain, C1q was increased and localized at synaptic terminals, causing the apposition of phagocytic microglia and ensuing synaptic engulfment. We further determined that neuronal Nr4a1 signaling was essential for attracting C1q synaptic

SUBMITTER: Han X 

PROVIDER: S-EPMC8854434 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature