Cx3cr1 deficiency alters renal-infiltrating immune cell transcriptional landscape in lupus-prone MRL/lpr mice 2274

Abstract Description Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by aberrant immune responses and chronic inflammation. CX3CR1, a chemokine receptor, plays a critical role in immune cell trafficking and lupus pathogenesis. We previously found that Cx3cr1 deficiency exacerbates murine lupus nephritis, but the mechanisms remain unclear. Using single-cell RNA sequencing (scRNA-seq), we analyzed renal-infiltrating CD45+ leukocytes from wild-type (WT) and Cx3cr1-knockout (KO) lupus-prone MRL/lpr mice. scRNA-seq revealed transcriptional changes in T cells, B cells, NK cells, neutrophils, monocytes, macrophages, and dendritic cells. In KO mice, macrophages exhibited upregulation of complement-related genes, including C1qa, C1qb, C1qc, and C3ar1, indicating enhanced complement activation. In addition, Egfr was upregulated in CD4 T cells, dendritic cells, B cells, NK cells, neutrophils, double negative T cells, and macrophages, suggesting a role for epidermal growth factor (EGF) in autoimmune activation and proliferation. Pathway analysis showed activation of complement, coagulation, and EGF-associated pathways in various immune cell subsets. These findings suggest that Cx3cr1 deficiency alters the transcriptional landscape of renal-infiltrating immune cells to exacerbate lupus nephritis in MRL/lpr mice. Topic Categories Basic Autoimmunity (BA)