Dynamically modeling the effective range of IL-2 dosage in the treatment of systemic lupus erythematosus

Highlights•Tcon/Treg ratio can be an indicator to define the IL-2 dosage therapeutic window in SLE treatment•SLE patients with high levels of self-antigen are predicted to have a narrow IL-2 therapeutic window•High-dose IL-2 should overactivate Tcons and increase the Tcon/Treg ratio in SLE patients•SLE patients with lower pre-treatment Treg are more likely to benefit from IL-2 administrationSummarySystemic lupus erythematosus (SLE) is a complex systemic autoimmune disease characterized by an overactive immune response to self-antigen. The overactivation of CD4+ Foxp3− conventional T cells (Tcons) and the inactivation of CD4+ CD25+ Foxp3+ regulatory T cells (Tregs) play important roles in the progression of SLE. Clinical trials showed that low-dose interleukin-2 (IL-2) is effective in treating SLE. Here, we developed a mathematical model involving Tcons, Tregs, natural killer (NK) cells, and IL-2 to simulate the dynamic processes involved in the treatment of SLE. We found an effective range of IL-2 dosage defined by the Tcon/Treg ratio in SLE treatment, termed the IL-2 dosage therapeutic window (IDTW). Our results showed that high levels of self-antigen result in a narrow IDTW and high post-treatment Tcon/Treg ratio. Furthermore, we proposed a classification method based on the ratio of pre-treatment Treg to CD4+ T cells to predict the treatment outcome of SLE patients.Graphical abstract