A Novel Microglia-Specific Transcriptional Signatures Correlates with Behavioural Deficits in Neuropsychiatric Lupus (NP-SLE)

Systemic lupus erythematosus (SLE) can present with neuropsychiatric manifestations, collectively termed NP-SLE. This study identifies a microglia-specific transcriptional signature in mouse models of NP-SLE. Through RNA-seq analysis of microglia and brain-infiltrating macrophages, we uncover an 18-gene 'NP-SLE signature' and its correlation with behavioral deficits. We also observe enrichment of genes associated with disease-associated microglia (DAM), which have been implicated in neurodegenerative diseases. These findings suggest a critical role for microglia-intrinsic mechanisms in the onset of NP-SLE and provide new insights into the cellular and molecular pathways driving this disease. Bulk RNA sequencing was performed on microglia and macrophages isolated by fluorescence-activated cell sorting (FACS) from brains of wild-type (WT - Casp8flox) and Caspase-8 Removed CD11c-specific Overactive MyD88 (CReCOM - CD11cCre Casp8flox) mice at young (5-6 months) and old (11-12 months) time points.