IL17: potential therapeutic target in Sjögren's syndrome using adenovirus-mediated gene transfer.
IL17: potential therapeutic target in Sjögren's syndrome using adenovirus-mediated gene transfer.
复制标题
DOI：
10.1038/labinvest.2010.164
复制
发表时间：
2011-01
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
--
作者：
干燥综合征（SS）涉及主要是唾液腺和泪腺的慢性进行性炎症，导致唾液和泪液水平降低，最终导致口干和干眼病。分泌IL 17 A的TH 17细胞群已显示在越来越多的自身免疫性疾病（包括SS）中起重要作用。在本研究中，我们研究了IL 17 A在SS发生和发作中的作用。通过逆行插管将表达IL 17 R：Fc融合蛋白或LacZ的腺病毒-5载体注射到6-8周龄（疾病前阶段）或15-17周龄（疾病阶段）之间的SS易感（SSS）C57 BL/6. NOD-Aec 1Aec 2小鼠的唾液腺中。随后对小鼠的SS表型进行表征。在7或16周龄时用Ad 5-IL 17 R：Fc病毒载体插管的小鼠表现出血清IL 17水平以及存在于其脾脏中的CD 4 + IL 17 + T细胞的总数的快速暂时但持续的降低。疾病分析表明，这些小鼠显示其唾液腺的淋巴细胞浸润减少，ANA库正常化，唾液分泌增加。相反，用对照Ad 5-LacZ病毒载体插管的小鼠没有表现出类似的变化，并且进展到明显的疾病阶段。Ad 5-IL 17 R：Fc阻断因子在SSS小鼠中减少SS病理的能力强烈表明IL 17是唾液腺功能障碍中的重要炎性细胞因子。因此，靶向IL 17的治疗方法可以有效预防腺体功能障碍。
Sjögren's syndrome (SS) involves a chronic, progressive inflammation primarily of the salivary and lacrimal glands leading to decreased levels of saliva and tears that eventually result in dry mouth and dry eye diseases. TH17 cell populations secreting IL17A have been shown to play an important role in an increasing number of autoimmune diseases, including SS. In the present study, we investigated the function of IL17A on SS development and onset. Adenovirus-5 vectors expressing either IL17R:Fc fusion protein or LacZ were injected via retrograde cannulation into the salivary glands of SS-susceptible (SSS) C57BL/6.NOD-Aec1Aec2 mice between 6-8 weeks of age (a pre-disease stage) or 15-17 weeks of age (a diseased stage). The mice were subsequently characterized for their SS phenotypes. Mice cannulated with the Ad5-IL17R:Fc viral vector at either 7 or 16 weeks of age exhibited a rapid temporal, yet persistent, decrease in the levels of serum IL17 as well as the overall numbers of CD4+IL17+ T cells present in their spleens. Disease profiling indicated that these mice showed decreased lymphocytic infiltrations of their salivary glands, normalization of their ANA repertoire, and increased saliva secretion. In contrast, mice cannulated with the control Ad5-LacZ viral vector did not exhibit similar changes and progressed to the overt disease stage. The capacity of the Ad5-IL17R:Fc blocking factor to reduce SS pathology in SSS mice, strongly suggest that IL17 is an important inflammatory cytokine in salivary gland dysfunction. Thus, therapeutic approach targeting IL17 may be an effective in preventing glandular dysfunction.