PDF(Pubmed)
Abstract：
UNASSIGNED: Defective interleukin-2 (IL-2) production contributes to immune system imbalance in patients with systemic erythematosus lupus (SLE). Recent clinical studies suggested that low-dose IL-2 treatment is beneficial for SLE and the therapeutic effect is associated with regulatory T cell (Treg) expansion. Pharmacological calcineurin inhibition induces a reduction in the number of Tregs because they require stimulation of T cell receptor signaling and IL-2 for optimal proliferation. However, the activation of T cell receptor signaling is partially dispensable for the expansion of Tregs, but not for that of conventional T cells if IL-2 is present.
UNASSIGNED: We examined whether addition of IL-2 restores the Treg proportion even with concurrent use of a calcineurin inhibitor and if the follicular helper T cell (Tfh) proportion is reduced in an SLE-like murine chronic graft versus host disease model.
UNASSIGNED: Using a parent-into-F1 model, we investigated the effect of IL-2 plus tacrolimus on Treg and Tfh proportions and the therapeutic effect.
UNASSIGNED: Treatment with a combination of IL-2 and tacrolimus significantly delayed the initiation of proteinuria and decreased the urinary protein concentration, whereas tacrolimus or IL-2 monotherapy did not significantly attenuate proteinuria. Phosphorylation of signal transducer and activator of transcription 3, a positive regulator of Tfh differentiation, was reduced by combination treatment, whereas phosphorylation of signal transducer and activator of transcription 5, a negative regulator, was not reduced.
UNASSIGNED: Addition of calcineurin inhibitors as adjunct agents may be beneficial for IL-2-based treatment of lupus nephritis.
UNASSIGNED: We examined whether addition of IL-2 restores the Treg proportion even with concurrent use of a calcineurin inhibitor and if the follicular helper T cell (Tfh) proportion is reduced in an SLE-like murine chronic graft versus host disease model.
UNASSIGNED: Using a parent-into-F1 model, we investigated the effect of IL-2 plus tacrolimus on Treg and Tfh proportions and the therapeutic effect.
UNASSIGNED: Treatment with a combination of IL-2 and tacrolimus significantly delayed the initiation of proteinuria and decreased the urinary protein concentration, whereas tacrolimus or IL-2 monotherapy did not significantly attenuate proteinuria. Phosphorylation of signal transducer and activator of transcription 3, a positive regulator of Tfh differentiation, was reduced by combination treatment, whereas phosphorylation of signal transducer and activator of transcription 5, a negative regulator, was not reduced.
UNASSIGNED: Addition of calcineurin inhibitors as adjunct agents may be beneficial for IL-2-based treatment of lupus nephritis.
摘要：
■白细胞介素-2（IL-2）的产生缺陷导致系统性红斑狼疮（SLE）患者的免疫系统失衡。最近的临床研究表明，低剂量IL-2治疗对SLE有益，治疗效果与调节性T细胞（Treg）扩增有关。药理学钙调磷酸酶抑制诱导Treg数量的减少,因为它们需要刺激T细胞受体信号传导和IL-2以实现最佳增殖。然而,T细胞受体信号的激活对于Tregs的扩增是部分可有可无的，但如果存在IL-2，则不适用于常规T细胞。
■我们研究了在SLE样小鼠慢性移植物抗宿主疾病模型中，即使同时使用钙调磷酸酶抑制剂，IL-2的添加是否恢复了Treg比例，以及滤泡辅助性T细胞（Tfh）比例是否降低。
■使用父入F1模型，我们研究了IL-2联合他克莫司对Treg和Tfh比例的影响以及治疗效果。
■用IL-2和他克莫司联合治疗显著延缓了蛋白尿的开始，降低了尿蛋白浓度，而他克莫司或IL-2单药治疗未显著减轻蛋白尿。信号转导和转录激活因子3的磷酸化，Tfh分化的正调节因子，通过联合治疗减少了，而信号转导和转录激活因子5的磷酸化，负调节因子，没有减少。
■添加钙调磷酸酶抑制剂作为辅助药物可能有益于基于IL-2的狼疮性肾炎的治疗。
■我们研究了在SLE样小鼠慢性移植物抗宿主疾病模型中，即使同时使用钙调磷酸酶抑制剂，IL-2的添加是否恢复了Treg比例，以及滤泡辅助性T细胞（Tfh）比例是否降低。
■使用父入F1模型，我们研究了IL-2联合他克莫司对Treg和Tfh比例的影响以及治疗效果。
■用IL-2和他克莫司联合治疗显著延缓了蛋白尿的开始，降低了尿蛋白浓度，而他克莫司或IL-2单药治疗未显著减轻蛋白尿。信号转导和转录激活因子3的磷酸化，Tfh分化的正调节因子，通过联合治疗减少了，而信号转导和转录激活因子5的磷酸化，负调节因子，没有减少。
■添加钙调磷酸酶抑制剂作为辅助药物可能有益于基于IL-2的狼疮性肾炎的治疗。
