Systemic lupus erythematosus (SLE) is a complex autoimmune disease involving dysregulation of various immune cells. Monocytes, as key components of the innate immune system, play a significant role in the inflammation and immune disruption of SLE, yet their precise mechanisms and therapeutic potential require systematic elucidation. This review aims to summarize the role of monocytes in the pathogenesis of SLE and explore their potential as novel therapeutic targets, providing insights for a deeper understanding of SLE and the development of targeted interventions.

This article is a literature review. By systematically retrieving and analyzing relevant domestic and international studies, it integrates the latest research progress on the biological characteristics of monocytes, their functional abnormalities in SLE, their association with clinical manifestations, and targeted therapeutic strategies. The reviewed content encompasses evidence from basic research, clinical observations, and clinical trials.

1. Multiple Functions of Monocytes: Derived from bone marrow, monocytes can be classified into three subsets based on surface markers: classical (CD14⁺⁺CD16^-), intermediate (CD14⁺⁺CD16⁺), and non-classical (CD14⁺CD16⁺). They possess multiple immune functions including phagocytosis, antigen presentation, cytokine secretion, and migratory recruitment, and can differentiate into macrophages or dendritic cells in tissues.

2. Role in SLE Pathogenesis: In SLE patients, monocytes exhibit significant abnormalities. The proportion of classical monocytes is increased and they highly express interferon-stimulated genes (ISGs), driving persistent type I interferon (IFN-I) signaling pathway activation, a core feature of SLE immune imbalance. Non-classical monocytes promote the differentiation of T helper 17 (Th17) cells. Monocytes also contribute to the immunopathology of SLE through epigenetic alterations (e.g., DNA methylation), secretion of pro-inflammatory cytokines (e.g., TNF-α, IL-6), and interactions with other immune cells (T cells, B cells).

3. Association with Clinical Manifestations: Monocytes are closely associated with SLE disease activity and organ damage. For instance, in lupus nephritis (LN), patrolling monocytes (PMos) play a key role in early renal inflammation. The proportion of certain monocyte subsets or the expression levels of specific molecules (e.g., IFITM3) correlate positively with SLE Disease Activity Index (SLEDAI) scores, suggesting their potential as biomarkers for disease activity. Furthermore, monocyte dysfunction is involved in the development of SLE-associated atherosclerosis.

4. Potential and Challenges as Therapeutic Targets: Strategies targeting monocytes show promise, such as using anti-CD40 monoclonal antibodies (e.g., BI655064) for LN, topical application of mupirocin to reduce cutaneous monocyte infiltration, or using fatty acid synthase (FASN) inhibitors to modulate macrophage activation. However, this strategy faces challenges, primarily due to the essential role of monocytes in normal immune defense; excessive inhibition may increase infection risk. Additionally, the high heterogeneity of monocytes makes achieving specific targeting of particular pathogenic subsets a current difficulty.

Monocytes are deeply involved in the pathogenesis and progression of SLE through various mechanisms, serving as a critical nexus connecting innate and adaptive immune dysregulation. In-depth analysis of the functions and regulatory networks of different monocyte subsets is crucial for elucidating SLE mechanisms and discovering new biomarkers. Although therapeutic strategies targeting monocytes have shown preliminary progress, future efforts must focus on developing more precise and specific immunotherapies. The goal is to effectively control SLE inflammation and organ damage while minimizing interference with normal immune function, thereby improving patient prognosis.