Medizinische Poliklinik-Innenstadt, Department of Dermatology and Allergology, University of Munich, Munich, Germany.
Nephrol Dial Transplant. 2012 Apr;27(4):1358-67. doi: 10.1093/ndt/gfr544. Epub 2011 Oct 10.
Systemic lupus erythematosus (SLE) is still treated with global immunosuppressants with serious toxicities. We hypothesized that endogenous immunosuppressive molecules might be able to control SLE manifestations more specifically. Heat shock protein 10, or chaperonin 10 (Cpn10), is a secretory molecule that can suppress innate and adaptive immunity.
Recombinant human Cpn10 (100 μg per mouse) was given intraperitoneally to healthy-appearing female MRL-(Fas)lpr mice from 12 to 22 weeks of age. At the age of 22 weeks, mice were analysed for treatment outcome by harvesting organs, plasma and urine.
Cpn10 entirely prevented cutaneous lupus lesions as compared to vehicle-treated mice. Cpn10 also suppressed lupus nephritis as evident from serum creatinine levels, albuminuria and the scores of disease activity and chronicity. Autoimmune lung disease was unaffected by Cpn10 treatment while overall survival of mice was prolonged. Cpn10 did not have any major effects on either dendritic cell or B-cell counts except T cells in spleen, plasma interferon-gamma, tumour necrosis factor-alpha, interleukin-10, anti-nuclear autoantibody levels or markers of lymphoproliferation.
In summary, recombinant Cpn10 selectively prevents cutaneous lupus and suppresses nephritis in MRL-(Fas)lpr mice without affecting the underlying systemic autoimmune process. Hence, Cpn10 might be useful for the treatment of skin and kidney manifestations of SLE.
系统性红斑狼疮（SLE）仍采用全身性免疫抑制剂治疗，但这些药物具有严重的毒性。我们假设内源性免疫抑制分子可能能够更特异性地控制 SLE 的表现。热休克蛋白 10 或伴侣蛋白 10（Cpn10）是一种分泌性分子，可抑制固有和适应性免疫。
将重组人 Cpn10（每只小鼠 100μg）从 12 至 22 周龄的健康外观雌性 MRL-（Fas）lpr 小鼠腹腔内给药。在 22 周龄时，通过收获器官、血浆和尿液来分析小鼠的治疗效果。
与载体处理的小鼠相比，Cpn10 完全预防了皮肤狼疮病变。Cpn10 还抑制了狼疮肾炎，表现为血清肌酐水平、蛋白尿以及疾病活动和慢性评分。自身免疫性肺疾病不受 Cpn10 治疗的影响，而小鼠的总生存率延长。Cpn10 除了脾内 T 细胞外，对树突状细胞或 B 细胞计数没有任何重大影响，对血浆干扰素-γ、肿瘤坏死因子-α、白细胞介素-10、抗核自身抗体水平或淋巴增生标志物也没有影响。
总之，重组 Cpn10 选择性地预防 MRL-（Fas）lpr 小鼠的皮肤狼疮，并抑制肾炎，而不影响潜在的系统性自身免疫过程。因此，Cpn10 可能对治疗 SLE 的皮肤和肾脏表现有用。
