TSLP-induced placental DC activation and IL-10+ NK cell expansion: Comparative study based on BALB/c × C57BL/6 and NOD/SCID × C57BL/6 pregnant models

Thymic stromal lymphopoietin (TSLP)–TSLP receptor (TSLP-R) interactions activate CD11c+ dendritic cells (DCs) and increase epithelial cell Th2-type cytokine production. We detected intracellular TSLP expression on CK7+ trophoblast cells and TSLP-R expression on placental DCs from pregnant BALB/c × C57BL/6 and NOD/SCID × C57BL/6 mice on gestational day 12.5. Murine recombinant TSLP activated DCs from BALB/c mice, with increased CD80 and CD83 expressions; TSLP-activated DCs induced IL-10-producing NK cell expansion. This was abrogated by anti-TSLP Ab or by culturing CD49b+ NK cells alone. No TSLP-DC-induced IL-10+CD49b+ cell expansion occurred when DCs and CD49b+ cells were cultured separately. Although TSLP-induced DC activation occurred in NOD/SCID mice, the IL-10+ NK cell percentage was unchanged. CK7+ trophoblast cells may activate placental DCs via a TSLP–TSLP-R interaction and induce DC-dependent placental NK cell IL-10 production. TSLP-DC and NK cell contact appears necessary for IL-10+CD49b+ cell expansion. Placental NK cells from NOD/SCID × C57BL/6 mice appear less sensitive to TSLP-DC induction.