Lin Yi, Wang Wenjing, Jin Haiyan, Zhong Yanmin, Di Jingfang, Zeng Shan, Saito Shigeru
Institute of Tissue Transplantation and Immunology, College of Life Science and Technology, Jinan University, Guangzhou 510632, China.
J Reprod Immunol. 2009 Jan;79(2):119-28. doi: 10.1016/j.jri.2008.10.001. Epub 2008 Dec 10.
We confirmed previously the existence of thymic stromal lymphopoietin (TSLP)-positive cells in murine placenta by flow cytometry. To compare the characteristics of Toll-like receptor 3 (TLR3)- and TSLP-mediated placental dendritic cell (DC) activation, pregnant BALB/c mouse mated with C57BL/6 male were used as a model of allogenic gestation. Placental CD11c(+) DCs were potently activated by the TLR3-agonist polyinosinic polycytidylic acid [poly (I:C)], subsequently causing increased expression of co-stimulatory molecules. Accordingly, increased intracellular production of interleukin (IL)-12 and interferon (IFN)-gamma, but not IL-4 or IL-10, were detected after stimulation by poly (I:C). In the case of TSLP-stimulation, although increased expression of co-stimulatory molecules was also detected, there was no substantial increase of intracellular production of IL-12, IFN-gamma, IL-4 or IL-10. In contrast, the expression of the Th2 cell-attracting chemokine, the thymus and activation-regulated chemokine (TARC) or CCL17, was significantly boosted in response to TSLP induction, whereas no significant increase of CCL17 was observed when triggering TLR3 with its specific agonist poly (I:C). The data were further supported by a CD4(+)IL-10(+) cell migratory assay. These results suggest that TSLP-TSLP receptor interaction may result in a Th2-type microenvironment at the feto-maternal interface by inducing the production of Th2 cell-attracting chemokine and modulating the immigration of Th2-type cells.
我们之前通过流式细胞术证实了小鼠胎盘中存在胸腺基质淋巴细胞生成素（TSLP）阳性细胞。为了比较Toll样受体3（TLR3）和TSLP介导的胎盘树突状细胞（DC）激活的特征，将与C57BL/6雄性小鼠交配的怀孕BALB/c小鼠作为同种异体妊娠模型。胎盘CD11c(+) DCs被TLR3激动剂聚肌苷酸聚胞苷酸[聚（I:C）]有效激活，随后导致共刺激分子表达增加。因此，在聚（I:C）刺激后，检测到细胞内白细胞介素（IL）-12和干扰素（IFN）-γ的产生增加，但IL-4或IL-10没有增加。在TSLP刺激的情况下，虽然也检测到共刺激分子表达增加，但细胞内IL-12、IFN-γ、IL-4或IL-10的产生没有实质性增加。相反，响应TSLP诱导，吸引Th2细胞的趋化因子、胸腺和激活调节趋化因子（TARC）或CCL17的表达显著增强，而用其特异性激动剂聚（I:C）触发TLR3时，未观察到CCL17有显著增加。CD4(+)IL-10(+)细胞迁移试验进一步支持了这些数据。这些结果表明，TSLP-TSLP受体相互作用可能通过诱导吸引Th2细胞的趋化因子产生和调节Th2型细胞的迁移，在母胎界面形成Th2型微环境。
