Investigating cellular dynamics and molecular pathways through single-cell RNA sequencing in an imiquimod-induced lupus-like model

Background Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by extensive immune cell dysregulation. The use of Imiquimod (IMQ), a topical immune response modifier, in animal models generates lupus-like symptoms, providing a valuable platform for probing the disease's mechanisms. Methods This study utilized single-cell RNA sequencing (scRNA-seq) to characterize the splenic cells from both IMQ-induced lupus model mice and control mice. Over 33,000 cells were analyzed and categorized into various immune cell subtypes based on gene expression markers. Results Our analysis of over 33,000 splenic cells from IMQ-induced lupus model and control mice revealed significant increases in the proportions of plasma cells, macrophages, and neutrophils in the lupus model. Further, B cell heterogeneity was dissected, revealing novel B cell subtypes and significant pathway enrichment related to B cell receptor signaling and cellular stress responses. In T cells, distinct subtype dynamics and pathway enrichments, including those associated with T cell activation and differentiation, were identified. Analysis of dendritic and neutrophil subtypes revealed specific transcriptional changes and pathway activations related to immune system processes. Lastly, enhanced cellular interactions and regulatory network analyses uncovered altered signaling pathways and key transcription factors like Foxp3, Lef1, and Cebpa, which are implicated in governing immune responses in lupus. Conclusion The application of scRNA-seq has unveiled the intricate immune landscape in lupus, demonstrating that IMQ-induced models effectively replicate key aspects of human lupus. The study not only enhances our understanding of lupus pathogenesis but also highlights potential targets for therapeutic intervention based on altered cell proportions, gene expression, and cell-cell interactions.