Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder characterized by immune system dysfunction, the production of autoantibodies, and multi-organ inflammation. Lupus nephritis (LN) is one of the most severe complications of this condition. Approximately 60% of patients with SLE develop LN, which leads to both increased morbidity and mortality. Furthermore, LN has the potential to progress to end-stage renal disease. Macrophages, key components of the innate immune system, are involved in the pathophysiology of LN through immune complex clearance, antigen presentation, regulation of inflammation, and tissue repair. Macrophage polarization into pro-inflammatory (M1) versus anti-inflammatory (M2) functional phenotypes is a component of LN disease progression. M1 macrophages are responsible for supporting pro-inflammatory immunity and promoting tissue damage, whereas M2 macrophages are necessary for tissue repair and resolution of inflammation. However, dysregulated M2 function may exacerbate the pathogenesis of LN, indicating the complex role of macrophages in LN. Novel therapeutic approaches associated with the mechanisms of macrophage polarization and/or macrophage signaling pathways have emerged as therapeutic targets to modify the progression of LN. Furthermore, proinflammatory cytokines enhance renal inflammation and autoimmunity; alternatively, anti-inflammatory cytokines play a dual role in LN, contributing positively and negatively to the disease process. The purpose of this review is to investigate the role of macrophages in the pathogenesis of LN and highlight macrophage-targeted therapies or biomarkers as diagnostic tools and new therapeutic avenues to improve long-term outcomes for patients.
Zhang et al. (2025) studied this question.