Effect of immune tolerance induced by immature dendritic cells and CTLA4-Ig on systemic lupus erythematosus: An in vivo study
Effect of immune tolerance induced by immature dendritic cells and CTLA4-Ig on systemic lupus erythematosus: An in vivo study
复制标题
未成熟树突状细胞和 CTLA4-Ig 诱导的免疫耐受对系统性红斑狼疮的影响：一项体内研究
DOI：
10.3892/etm.2018.5697
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发表时间：
2018-03-01
影响因子：
2.7
通讯作者：
Lin, You-Kun
中科院分区：
文献类型：
--
作者：
Huang, Cuili;Zhang, Lidan;Lin, You-Kun
系统性红斑狼疮（SLE）是一种多器官自身免疫性疾病，其组织损伤由自身抗体引起。特异性免疫耐受的诱导，包括免疫调节细胞的利用，可能会增强器官移植对SLE患者的治疗效果。此外，据报道，抑制免疫反应是SLE的有效治疗方法。然而，很少有研究探讨SLE治疗中免疫耐受增加和免疫反应降低之间的关系。树突状细胞（dc）是一种高效的抗原呈递细胞，能够诱导特异性耐受，而细胞毒性T淋巴细胞抗原4-免疫球蛋白（CTLA4-Ig）抑制免疫反应。本研究将白细胞介素(IL)-10处理的dc和CTLA4-Ig单独或联合给予SLE小鼠，观察其治疗效果。在骨髓源性dc的培养基中加入IL-10，阻止其向成熟细胞分化。主要组织相容性复合体II、cd40、CD80和CD86的表达水平均较低，表明树突状细胞仍处于未成熟状态。随后将il -10处理的树突状细胞注射到B6尾静脉。MRL-Fas(lpr)/J狼疮小鼠，这是SLE建立的动物模型。为了扩大耐受性，小鼠同时注射CTLA4-Ig。与il -10处理DC和CTLA4-Ig组相比，il -10处理DC和CTLA4-Ig联合治疗强烈诱导SLE小鼠免疫耐受，尿蛋白、抗核抗体、双链DNA和IL-17A水平显著降低。T辅助细胞比例显著降低，CD4（+）叉头盒蛋白P3(+) Treg细胞比例显著升高，进一步证实了免疫耐受的诱导作用。这些结果表明，il -10- dc和CTLA4-Ig联合治疗可能是治疗SLE的一种有希望的新治疗策略。
Systemic lupus erythematosus (SLE) is a multi-organ autoimmune disease in which tissue damage is caused by autoantibodies. The induction of specific immune tolerance, including the utilization of immune regulatory cells, may enhance the therapeutic effects of organ transplantation in patients with SLE. Furthermore, inhibiting immune responses has been reported to be an effective treatment for SLE. However, few studies have explored the association between an increased immune tolerance and a decreased immune response in SLE treatment. Dendritic cells (DCs), which are highly efficient antigen-presenting cells, are able to induce specific tolerance, while cytotoxic T lymphocyte antigen 4-immunoglobulin (CTLA4-Ig) inhibits the immune response. In the present study, interleukin (IL)-10-treated DCs and CTLA4-Ig were administered to mice with SLE alone or in combination and the therapeutic effects were investigated. IL-10 was added into the culture medium of bone marrow-derived DCs to prevent them from differentiating into mature cells. Low levels of major histocompatibility complex II, cluster of differentiation (CD) 40, CD80 and CD86 were detected, which indicated that the immature state of DCs was maintained. IL-10-treated DCs were subsequently injected into the caudal vein of B6. MRL-Fas(lpr)/J lupus mice, which are an established animal model of SLE. To amplify the tolerance effect, mice were simultaneously injected with CTLA4-Ig. Compared with the IL-10-treated DC and CTLA4-Ig groups, combined treatment with IL-10-treated DCs and CTLA4-Ig strongly induced immune tolerance in mice with SLE, as indicated by the significantly reduced levels of urine protein, anti-nuclear antibody, double-stranded DNA and IL-17A. A significant decrease in the proportion of T helper cells and an increase in the proportion of CD4(+) forkhead box protein P3(+) Treg cells was also observed, further confirming the induction of immune tolerance. These results suggest that combined treatment with IL-10-DCs and CTLA4-Ig may be a promising novel therapeutic strategy for the treatment of SLE.