Dendritic-cell subset devotes to the chaos of programmed cell-death patterns from systemic lupus erythematosus to lupus nephritis

Abstract

Abstract Abnormal programmed cell death of immune cells relates to autoimmune diseases, but the programmed cell death pattern conditions in systemic lupus erythematosus (SLE), especially lupus nephritis (LN), remain unclear. We analyzed bulk RNA-sequencing database and single-cell RNA sequencing (scRNA-seq) profile from SLE peripheral blood mononuclear cells (PBMCs). Besides, we ran renal tissue scRNA-seq from LN patients and normal controls collected in our hospital. There was an imbalance among three cell-death patterns both in SLE and LN: pro-inflammatory patterns pyroptosis and necroptosis were activated, but anti-inflammatory pattern apoptosis was inhibited. Additionally, we found that the cell-death pattern imbalance could be largely attributed to dendritic cell (DC) subsets, among which CLEC9A + cDC1 is a key subgroup devoting to it. This DC subgroup in LN renal tissue has peripheral circulatory origin. Additionally, we sorted out STING to be the upstream factor regulating three cell-death patterns in SLE. Therefore, we provided a novel insight for the role of DC subset in the cell-death patterns imbalance in the pathogenesis of SLE and LN.