Rationale: Regulatory T (Treg) cells suppress autoimmunity and restrain inflammatory responses, showing promising potential in autoimmune glomerulonephritis (GN) therapy with minimizing nonspecific immunosuppression. Although low-dose interleukin-2 (IL-2) has been shown to promote Treg expansion, its clinical utility is constrained by its short half-life and concurrent effector T cell activation. Methods: An IL-2 mutein STS718 was engineered by introducing point mutations and fusing it to a human IgG1 Fc domain. The molecular characteristics of STS718, including its affinity, selectivity, and half-life were evaluated. Results: STS718 exhibited a lower affinity for IL-2 receptor (IL-2Rβγ) and comparable affinity for IL-2Rαβγ compared with wild-type IL-2-Fc of human, rat, and mouse, as well as a prolonged half-life. STS718 expanded Treg cells in mice and cynomolgus monkeys in a manner that was dependent on either time or dose, without significantly affecting the effector T cell activation. Proof-of-concept experiments confirmed that sustained Treg expansion mediated by STS718 effectively suppressed the progression of autoimmune GN models, exhibiting superior efficacy compared to wild-type IL-2-Fc. In addition, the STS718 was capable of inducing the expansion of human functional Treg cells from either naïve CD4 Conclusions: Collectively, these findings suggest that engineered IL-2 mutein which selectively expands Treg cells