Cxcl9macrophages recruit circulating Cxcr3+ plasmablasts into kidneys to promote pathogenesis of lupus nephritis mice.

Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disease driven by autoantibody production. Lupus nephritis (LN), a severe SLE complication, is primarily caused by renal autoantibodies. Long-lived plasma cells (LLPCs), the main producers of these autoantibodies, are especially elevated in the kidney of LN patients, particularly in refractory or recurrent cases. However, the cause of increased LLPCs in LN kidneys remains unknown. This study uses an LN mouse model and combines single-cell RNA sequencing with spatial transcriptomics, finding that kidney-resident Cxcl9macrophages and their secreted chemokine Cxcl9 significantly rise with disease progression. This increase in Cxcl9 attracts Cxcr3+ plasmablasts in peripheral blood into the kidneys, where they differentiate into LLPCs and produce autoantibodies. Based on these findings, this study suggests that Cxcl9macrophages are the inducing factor causing the increase of LLPCs in LN kidneys and may be a potential therapeutic target for LN.