Bioinformatic analysis and experimental verification reveal expansion of monocyte subsets with an interferon signature in systemic lupus erythematosus patients

Arthritis Research & Therapy, Journal Year: 2025, Volume and Issue: 27(1)

Published: April 25, 2025

Systemic lupus erythematosus (SLE) is a complex autoimmune disorder characterized by chronic inflammation and multi-organ damage. A central factor in SLE pathogenesis the excessive production of type I interferon (IFN-I), which drives immune dysregulation. Monocytes, key components system, significantly contribute to IFN-I production. However, their specific roles remain incompletely understood. This study utilized bioinformatics statistical analyses, including robust rank aggregation (RRA), DESeq2, limma, analyze transcriptome data from peripheral blood mononuclear cells (PBMCs) monocytes patients healthy controls. Single-cell RNA sequencing (scRNA-seq) were processed using Seurat R package identify characterize monocyte subsets with strong IFN-driven gene signature. Flow cytometry was employed validate findings, markers such as CD14, SIGLEC1, IRF7 confirm subset composition. Our research has found that undergo transcriptional reprogramming, upregulation signature genes (ISGs), forming SLE-Related Monocyte Signature (SLERRAsignature). Moreover, composition phagocyte changes, an increase trend proportion CD14Mono8 flare group. The differentially expressed (DEGs) 13 are mainly ISGs, expression ISGs higher severe patients. We identified SIGLEC1+IRF7+ among these for first time discovered this group individuals. In SLE, enrichment score set representing positively correlated severity SLE. Finally, flow confirmed frequency CD14+SIGLEC1+IRF7+ PBMCs compared expansion IFN-I-producing subsets, particularly subset, plays crucial role pathogenesis. may serve potential biomarker therapeutic target managing

Language: Английский

Chronic Low-Level IFN-γ Expression Disrupts Mitochondrial Complex I Activity in Renal Macrophages: An Early Mechanistic Driver of Lupus Nephritis Pathogenesis

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 26(1), P. 63 - 63

Published: Dec. 25, 2024

Mitochondrial dysfunction and macrophage dysregulation are well recognized as significant contributors to the pathogenesis of autoimmune diseases. However, detailed mechanisms connecting these two factors remain poorly understood. This study hypothesizes that low but chronic interferon-gamma (IFN-γ) plays a critical role in processes. To explore this, we utilized ARE-Del mice, model characterized by sustained low-level IFN-γ expression lupus nephritis (LN)-like symptoms. Age- tissue-dependent gene analyses mice revealed suppression mitochondrial complex I components activities, particularly kidneys. The genotype-dependent indicates early disruption, which leads dysfunction. Notably, remission restored isolated renal macrophages from NZB/W lupus-prone mice. These findings suggest disrupts activity macrophages, highlighting its diseases like nephritis. provides new insights into molecular interactions underlying suggests potential targets for therapeutic intervention.

Language: Английский