Inflammatory stimuli accelerate Sjogren's syndrome-like disease in (NZB x NZW)F1 mice
Inflammatory stimuli accelerate Sjogren's syndrome-like disease in (NZB x NZW)F1 mice
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DOI：
10.1002/art.23368
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发表时间：
2008-05-01
影响因子：
--
通讯作者：
Fu, Shu Man
中科院分区：
文献类型：
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作者：
Deshmukh, Umesh S.;Ohyama, Yukiko;Fu, Shu Man
目标。本研究旨在确定全身性炎症的诱导是否会加速遗传易感小鼠干燥综合征（SS）的发展。雌性（NZB X NZW）F-1小鼠每隔一个月接受一次弗氏不完全佐剂（IFA）或磷酸盐缓冲盐水（PBS）治疗。通过测量匹罗卡品诱导的唾液量来监测唾液腺功能。在不同时间点处死小鼠，检查涎腺炎和涎腺浸润细胞。分析血清中唾液腺抗原、核抗原和ro60的自身抗体。在初始治疗7周后，ifa处理的小鼠唾液分泌明显减少，而pbs处理的对照组唾液分泌直到17周才减少。7周时，两组患者涎腺炎的严重程度及浸润唾液腺的T细胞和B细胞数量无显著差异。然而，在这个时间点，经ifa处理的小鼠唾液腺中CD11c（低）、B220+、Ly6C+、小鼠PDCA-1+树突状细胞（dc）的频率明显更高。虽然两组之间的自身抗体水平在早期时间点没有差异，但到晚期时间点，经ifa处理的小鼠的自身抗体水平较高。在早期时间点观察到的ifa治疗小鼠的腺体功能障碍与涎腺炎的严重程度或自身抗体水平无关。相反，它与腺体浆细胞样dc的频率增加有关。我们的数据表明，在（NZB x NZW）F-1小鼠中，广泛的炎症刺激可以加速SS样疾病的发展，并且SS中的腺体功能障碍可以在产生强大的适应性自身免疫反应之前发展。
Objective. This study was undertaken to determine whether induction of systemic inflammation accelerates the development of Sjogren's syndrome (SS) in genetically susceptible mice.Methods. Female (NZB X NZW)F-1 mice were treated with either Freund's incomplete adjuvant (IFA) or phosphate buffered saline (PBS) at monthly intervals. Salivary gland function was monitored by measuring pilocarpine-induced saliva volume. Mice were killed at different time points and examined for sialadenitis and salivary gland-infiltrating cells. Sera were analyzed for autoantibodies to salivary gland antigens, nuclear antigens, and Ro60.Results. While IFA-treated mice had significantly decreased salivary secretion 7 weeks after the initial treatment, salivary secretion did not decrease in PBS-treated controls until 17 weeks. At 7 weeks, the severity of sialadenitis and the number of T and B cells infiltrating the salivary glands did not differ between the 2 groups. However, at this time point IFA-treated mice showed significantly higher frequencies of CD11c(low), B220+, Ly6C+, mouse PDCA-1+ dendritic cells (DCs) in the salivary glands. While levels of autoantibodies did not differ between the 2 groups at early time points, by late time points IFA-treated mice had higher levels. The gland dysfunction observed in IFA-treated mice at earlier time points did not correlate with the severity of sialadenitis or levels of autoantibodies. Instead, it was associated with increased frequency of plasmacytoid DCs in the gland.Conclusion. Our data suggest that generalized inflammatory stimuli can accelerate the development of SS-like disease in (NZB x NZW)F-1 mice, and that gland dysfunction in SS can develop prior to the generation of a robust adaptive autoimmune response.