Single-Cell Sequencing Informs That Mesenchymal Stem Cell Alleviates Renal Injury Through Regulating Kidney Regional Immunity in Lupus Nephritis

Lupus nephritis (LN) is the common complication of systemic lupus erythematosus. The pathogenesis of LN kidney injury is unclear. In addition to systemic (extrarenal) immune cells, local (intrarenal) immune cells residing in "kidney regional immunity" are momentous in LN. Mesenchymal stem cell (MSC) therapy is effective for LN. However, mechanisms of MSC therapy remains unclear. In this study, we first systematically investigated the effects of MSC on immune cells in kidney regional immunity in LN using single-cell sequencing. We found that MSC reduced proinflammatory central memory CD4⁺ T cells, cytotoxic tissue-resident memory CD8⁺ T cells and exhausted CD8⁺ T cells, increased anti-inflammatory Naive/Effector CD8⁺ T cells and type 1 regulatory T cells; reduced infiltrating proinflammatory Ly6c hi/inter/lo era2⁺ macrophages, increased anti-inflammatory resident macrophage and Ly6c lo ear2^- macrophage; and reduced long-lived plasma cells and proinflammatory neutrophils and dendritic cells. This study laid a foundation for clinical applications of MSC.