The dual role of IL-2 in systemic lupus erythematosus: balancing pro-inflammatory and anti-inflammatory effects

Abstract

<p>Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by chronic inflammation and immune dysregulation. Interleukin-2 (IL-2), a central cytokine in T-cell biology, plays a paradoxical role in SLE pathogenesis. On one hand, it promotes effector T cell and natural killer (NK) cell activity, thereby amplifying inflammation; on the other, it supports the expansion and function of regulatory T cells (Tregs), which are essential for maintaining immune tolerance. This dual functionality makes IL-2 a driver of autoimmunity and a potential immunotherapeutic target. This review outlines the molecular mechanisms underlying IL-2's pro- and anti-inflammatory roles in SLE, highlights the regulatory factors that shape its functional balance, such as receptor affinity, dosing, exposure duration, and the immune microenvironment, and discusses recent progress in low-dose IL-2therapy and engineered IL-2 variants. A comprehensive understanding of IL-2 signaling dynamics is essential for the designing development of precision therapies designed to restore immune homeostasis in SLE.</p>