Li Xue, Lu Xiaoxiao, Sun Deming, Wang Xilian, Yang Liyuan, Zhao Shaozhen, Nian Hong, Wei Ruihua
Tianjin Medical University Eye Hospital, Eye Institute & School of Optometry and Ophthalmology, Tianjin, China.
Doheny Eye Institute, and Department of Ophthalmology, David Geffen School of Medicine, University of California Los Angeles (UCLA), Los Angeles, California, United States.
Invest Ophthalmol Vis Sci. 2016 Oct 1;57(13):5161-5170. doi: 10.1167/iovs.15-17824.
To investigate the immunoregulatory roles of adipose-derived mesenchymal stem cells (ADSCs) in autoimmune dacryoadenitis.
Rabbits were treated with ADSCs or phosphate-buffered solution on days 1, 3, 5, 7, and 9 after injection of activated peripheral blood lymphocytes, and clinical scores were determined by assessing tear production, break-up time, and fluorescein and hematoxylin and eosin staining. Inflammatory response was determined by measuring the expression of different mediators of inflammation in the lacrimal glands. The Th1/Th17-mediated autoreactive responses were evaluated by determining the proliferative response and the expression of cytokine genes and the lineage-determining transcription factors. The frequency of regulatory T cells (Tregs) was also examined.
The ADSC-treated rabbits showed decreased autoimmune responses, and the secretory function of their lacrimal gland was restored significantly. Treatment with ADSCs downregulated the Th1 and Th17 responses but enhanced Tregs function. In addition, ADSC treatment noticeably suppressed the expression of matrix metalloproteinase (MMP)-9, MPP-2, IL-1β, and IL-6, whereas it enhanced the expression of the anti-inflammatory cytokine IL-10.
Our results demonstrated that ADSC administration efficiently ameliorates autoimmune dacryoadenitis mainly via modulating Th1/Th17 responses.
研究脂肪来源间充质干细胞（ADSCs）在自身免疫性泪腺炎中的免疫调节作用。
在注射活化外周血淋巴细胞后的第1、3、5、7和9天，用ADSCs或磷酸盐缓冲溶液处理兔子，并通过评估泪液分泌、泪膜破裂时间以及荧光素和苏木精-伊红染色来确定临床评分。通过测量泪腺中不同炎症介质的表达来确定炎症反应。通过测定增殖反应、细胞因子基因表达和谱系决定转录因子来评估Th1/Th17介导的自身反应性。还检测了调节性T细胞（Tregs）的频率。
经ADSCs处理的兔子自身免疫反应降低，泪腺分泌功能明显恢复。ADSCs治疗下调了Th1和Th17反应，但增强了Tregs功能。此外，ADSCs治疗显著抑制了基质金属蛋白酶（MMP）-9、MPP-2、IL-1β和IL-6的表达，而增强了抗炎细胞因子IL-10的表达。
我们的结果表明，ADSCs给药主要通过调节Thl/Th17反应有效改善自身免疫性泪腺炎。
