Gao Xin, He Jing, Sun Xiaolin, Li Fangting
Center for Quantitative Biology, Peking University, Beijing 100871, China.
School of Physics, Peking University, Beijing 100871, China.
iScience. 2022 Aug 11;25(9):104911. doi: 10.1016/j.isci.2022.104911. eCollection 2022 Sep 16.
Systemic 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.
系统性红斑狼疮(SLE)是一种复杂的系统性自身免疫性疾病,其特征是对自身抗原的免疫反应过度活跃。CD4 Foxp3常规T细胞(Tcons)的过度激活和CD4 CD25 Foxp3调节性T细胞(Tregs)的失活在SLE的进展中起重要作用。临床试验表明,低剂量白细胞介素-2(IL-2)对治疗SLE有效。在此,我们建立了一个涉及Tcons、Tregs、自然杀伤(NK)细胞和IL-2的数学模型,以模拟SLE治疗中涉及的动态过程。我们发现了SLE治疗中由Tcon/Treg比率定义的IL-2剂量有效范围,称为IL-2剂量治疗窗口(IDTW)。我们的结果表明,高水平的自身抗原会导致较窄的IDTW和较高的治疗后Tcon/Treg比率。此外,我们提出了一种基于治疗前Treg与CD4 T细胞比率的分类方法,以预测SLE患者的治疗结果。