Eli and Edythe L, Broad Institute, 7 Cambridge Center, Cambridge, MA 02142, USA.
Arthritis Res Ther. 2010;12(6):R220. doi: 10.1186/ar3207. Epub 2010 Dec 23.
Sjögren's syndrome (SS) involves a chronic, progressive inflammation primarily of the salivary and lacrimal glands leading to decreased levels of saliva and tears resulting in dry mouth and dry eye diseases. Seminal findings regarding TH17 cell populations that secrete predominantly interleukin (IL)-17A 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 IL-17A on the development and onset of SS.
Adenovirus serotype 5 (Ad5) vectors expressing either IL-17A or LacZ were infused via retrograde cannulation into the salivary glands of C57BL/6J mice between 6 and 8 weeks of age or between 15 and 17 weeks of age. The mice were characterized for SS phenotypes.
Disease profiling indicated that SS-non-susceptible C57BL/6J mice whose salivary glands received the Ad5-IL17A vector developed a SS-like disease profile, including the appearance of lymphocytic foci, increased cytokine levels, changes in antinuclear antibody profiles, and temporal loss of saliva flow.
Induction of SS pathology by IL-17A in SS-non-susceptible mice strongly suggests that IL-17A is an important inflammatory cytokine in salivary gland dysfunction. Thus, localized anti-IL17 therapy may be effective in preventing glandular dysfunction.
干燥综合征（SS）涉及一种主要影响唾液腺和泪腺的慢性、进行性炎症，导致唾液和泪液水平下降，导致口干和干眼病。TH17 细胞群分泌主要白细胞介素（IL）-17A 的发现，已被证明在越来越多的自身免疫性疾病中发挥重要作用，包括 SS。在本研究中，我们研究了 IL-17A 对 SS 发展和发病的作用。
腺病毒血清型 5（Ad5）载体通过逆行插管在 6 至 8 周龄或 15 至 17 周龄之间输注到 C57BL/6J 小鼠的唾液腺中，表达 IL-17A 或 LacZ。对小鼠进行 SS 表型特征分析。
疾病分析表明，接受 Ad5-IL17A 载体的唾液腺的 SS 不易感 C57BL/6J 小鼠发展出类似于 SS 的疾病特征，包括淋巴细胞灶的出现、细胞因子水平升高、抗核抗体谱的变化以及唾液流量的暂时丧失。
IL-17A 在 SS 不易感小鼠中诱导 SS 病理学强烈表明 IL-17A 是唾液腺功能障碍中的一种重要炎症细胞因子。因此，局部抗 IL17 治疗可能有效预防腺体功能障碍。
