Comparison of murine thymic stromal lymphopoietin- and polyinosinic polycytidylic acid-mediated placental dendritic cell activation

Abstract 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)-γ, 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-γ, 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.