Agent-Based Modeling of Cutaneous Lupus Erythematosus: Exploring Keratinocyte-Driven Mechanisms

Systemic Lupus Erythematosus (SLE) is a complex autoimmune disease characterized by the immune system attacking the body’s own tissue, losing its ability to distinguish between foreign pathogens and healthy cells. This condition affects approximately 5 million individuals worldwide, leading to widespread tissue and organ damage, including the skin, joints, kidneys, cardiovascular system, and central nervous system. The pathology of SLE is influenced by a variety of predisposing factors such as genetic and epigenetic changes, environmental triggers, infections, and hormonal imbalances. One subtype of SLE is Cutaneous Lupus Erythematosus (CLE), where skin involvement serves as a significant manifestation of the disease. CLE is characterized by distinct serological and histological features, with ultraviolet (UV) radiation being a primary environmental trigger exacerbating disease severity. Epidemiological data indicate an annual incidence of approximately 4 cases per 100,100 persons for CLE, while 70–80% of SLE patients report skin involvement. In this work, we extend the capabilities of the Universal Immune System Simulator (UISS), an agent-based modeling framework, by incorporating a disease layer to simulate SLE progression with a focus on CLE. This enhancement emphasizes the role of keratinocytes in disease development, offering deeper insights into the mechanisms underlying CLE pathology.