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  • 标题:Dynamically modeling the effective range of IL-2 dosage in the treatment of systemic lupus erythematosus
  • 本地全文:下载
  • 作者:Xin Gao ; Jing He ; Xiaolin Sun
  • 期刊名称:iScience
  • 印刷版ISSN:2589-0042
  • 出版年度:2022
  • 卷号:25
  • 期号:9
  • 页码:1-25
  • DOI:10.1016/j.isci.2022.104911
  • 语种:English
  • 出版社:Elsevier
  • 摘要:SummarySystemic 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 abstractDisplay OmittedHighlights•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 administrationImmunology; Bioinformatics; Mathematical biosciences
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