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

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 rol...

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Detalles Bibliográficos
Autores principales: Gao, Xin, He, Jing, Sun, Xiaolin, Li, Fangting
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9429801/
https://www.ncbi.nlm.nih.gov/pubmed/36060072
http://dx.doi.org/10.1016/j.isci.2022.104911
Descripción
Sumario: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.