Clinically, IL-2-based Treg support shows promise yet mixed signals: in systemic lupus erythematosus (SLE), Tregs display exhaustion-like programs and type-I-IFN-driven coinhibitory networks that blunt function, helping explain the variable efficacy of standalone low-dose IL-2 and arguing for combinations that also ease metabolic stress. Here, IL2 is linked to systemic lupus erythematosus.