OBJECTIVE To address whether a targeted modulation of the abnormal expression of Hsp70 and autoantibodies against this molecule in systemic lupus erythematosus can influence disease. METHODS Lupus-prone (NZB × NZW)F1 mice that had been DNA-vaccinated with plasmids encoding Hsp70 and controls were monitored for lupus disease parameters including anti-double stranded DNA (anti-dsDNA) autoantibodies and cytokines using enzyme-linked immunosorbent assay, and for kidney function and pathology. The phenotypic and numerical changes in relevant immune cells were evaluated by flow cytometry, and cell function was assessed. RESULTS Mice that had been DNA-vaccinated with Hsp70 displayed marked suppression of anti-dsDNA antibody production, reduced renal disease, and antiinflammatory responses that are associated with a significantly extended survival, compared to controls. These protective effects in Hsp70-vaccinated mice were associated with an induction of tolerogenic immune responses and an expansion of functional Treg cells. CONCLUSION DNA vaccination with Hsp70 suppresses murine lupus by inducing tolerogenic immune responses and antiinflammatory immune responses associated with reduced disease manifestations and increased mouse survival.

中文翻译：

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用 Hsp70 接种 DNA 疫苗可预防 (NZB × NZW)F1 小鼠中的系统性红斑狼疮。

目的 探讨系统性红斑狼疮中 Hsp70 异常表达和针对该分子的自身抗体的靶向调节是否会影响疾病。方法 使用酶联免疫吸附试验监测已用编码 Hsp70 的质粒和对照进行 DNA 接种的易患狼疮 (NZB × NZW) F1 小鼠的狼疮疾病参数，包括抗双链 DNA (anti-dsDNA) 自身抗体和细胞因子，并用于肾功能和病理学。通过流式细胞术评估相关免疫细胞的表型和数值变化，并评估细胞功能。结果 用 Hsp70 接种 DNA 的小鼠表现出显着抑制抗 dsDNA 抗体产生、减少肾脏疾病和与显着延长生存期相关的抗炎反应，与对照相比。接种 Hsp70 的小鼠中的这些保护作用与致耐受性免疫反应的诱导和功能性 Treg 细胞的扩增有关。结论 Hsp70 DNA 疫苗接种通过诱导耐受性免疫反应和抗炎免疫反应来抑制鼠狼疮，这与减少疾病表现和增加小鼠存活率相关。