SLE 患者中 sIL-2Rα 的增加导致 IL-2 生物功能受阻和 Treg 细胞分化，这与 sIL-2Rα 与 IL-2 的结合有关。
Increased sIL-2Rα leads to obstruction of IL-2 biological function and Treg cells differentiation in SLE patients binding to IL-2.
机构信息
Department of Clinical Laboratory, The First Affiliated Hospital of Nanchang University, Nanchang, China.
出版信息
Front Immunol. 2022 Sep 20;13:938556. doi: 10.3389/fimmu.2022.938556. eCollection 2022.
BACKGROUND
The decrease of IL-2 level is believed to play an important role in the disease occurrence and development of SLE, but the relevant mechanisms have not been fully clarified. Many studies have found that the level of soluble interleukin 2 receptor α (sIL-2Rα) in SLE patients is significantly increased. Considering the fact that sIL-2Rα has the ability to bind IL-2, we want to know whether the increased sIL-2Rα has some impact on the level and function of IL-2 in SLE patients.
METHODS
New onset SLE patients, treated SLE patients and healthy volunteers were recruited. The levels of serum IL-2, IL-2 mRNA in CD3 T cells and serum sIL-2Rα were detected and compared in these subjects. Two mixed solid-phase sandwich ELISA system were designed to measure exclusively the heterodimers complex of sIL-2Rα/IL-2. The sera from SLE patients were pretreated with or without immune complex dissociation solution and detected for IL-2 levels. IL-2 standard or serum from HCs were used to co-incubate with recombinant sIL-2Rα or serum samples with high levels of sIL-2Rα and detected for IL-2 levels by ELISA. The inhibitory effect of sIL-2Rα on IL-2 biological activity was investigated by CTLL-2 cell proliferation assay. The frequencies and absolute counts of Treg cells were detected by flow cytometry before and after the addition of recombinant sIL-2Rα.
RESULTS
The levels of serum IL-2 in SLE patients were significantly decreased and negatively correlated with SLEDAI. However, there was no significant difference in IL-2 mRNA levels in CD3 T cells between SLE patients and healthy controls. The levels of serum sIL-2Rα in SLE patients were significantly increased, positively correlated with the SLEDAI and negatively correlated with the levels of serum IL-2. sIL-2Rα was shown to bind to IL-2 to form immune complex, resulting in false reduction in the detection level of serum IL-2 and significant decrease in biological activity of IL-2. The increase of sIL-2Rα was demonstrated to be one of the important mechanisms for the obstruction of Treg cells differentiation in SLE patients.
CONCLUSION
Increased serum sIL-2Rα can bind to IL-2, leading to obstruction of IL-2 activity and Treg cells differentiation.
背景
白细胞介素 2（IL-2）水平的降低被认为在系统性红斑狼疮（SLE）的发病和发展中起着重要作用，但相关机制尚未完全阐明。许多研究发现，SLE 患者可溶性白细胞介素 2 受体α（sIL-2Rα）水平显著升高。考虑到 sIL-2Rα 具有结合 IL-2 的能力，我们想知道增加的 sIL-2Rα 是否会对 SLE 患者的 IL-2 水平和功能产生影响。
方法
招募新诊断的 SLE 患者、治疗中的 SLE 患者和健康志愿者。检测并比较这些受试者血清中 IL-2、CD3 T 细胞中 IL-2mRNA 和血清 sIL-2Rα 的水平。设计了两种混合固相夹心 ELISA 系统，专门用于测量 sIL-2Rα/IL-2 的异二聚体复合物。用免疫复合物解离液预处理或不预处理 SLE 患者的血清，检测 IL-2 水平。用 IL-2 标准品或健康对照者（HCs）血清与重组 sIL-2Rα 共孵育，或用高浓度 sIL-2Rα 的血清样本共孵育，用 ELISA 检测 IL-2 水平。通过 CTLL-2 细胞增殖试验研究 sIL-2Rα 对 IL-2 生物学活性的抑制作用。加入重组 sIL-2Rα 前后，通过流式细胞术检测 Treg 细胞的频率和绝对计数。
结果
SLE 患者血清 IL-2 水平显著降低，与 SLEDAI 呈负相关。然而，SLE 患者和健康对照组之间 CD3 T 细胞中 IL-2mRNA 水平无显著差异。SLE 患者血清 sIL-2Rα 水平显著升高，与 SLEDAI 呈正相关，与血清 IL-2 水平呈负相关。sIL-2Rα 与 IL-2 结合形成免疫复合物，导致血清 IL-2 检测水平假性降低，IL-2 生物学活性显著降低。sIL-2Rα 的增加被证明是 SLE 患者 Treg 细胞分化受阻的重要机制之一。
结论
血清 sIL-2Rα 增加可与 IL-2 结合，导致 IL-2 活性和 Treg 细胞分化受阻。
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