Thymic stromal lymphopoietin from trophoblasts induces dendritic cell–mediated regulatory TH2 bias in the decidua during early gestation in humans

Abstract

Abstract Thymic stromal lymphopoietins (TSLPs) play critical roles in dendritic cell–mediated immune responses. In this study, we found that human trophoblasts and decidual epithelial cells in maternal-fetal interface of early placentas express TSLP mRNA and protein, but only trophoblast cells secret soluble TSLP. Human decidual CD1c+ DCs (dDCs) highly express the functional TSLP receptor complex TSLP receptor and interleukin-7 receptor-α. Recombinant human TSLP activates CD1C+ decidual DCs and peripheral monocyte-derived DCs with increased costimulatory molecules, major histocompatibility complex class II, and OX-40L. Human TSLP or supernatants from human trophoblasts specifically stimulate dDCs to highly produce interleukin-10 and TH2-attracting chemokine CCL-17. The TSLP-activated dDCs prime decidual CD4+ T cells for TH2 cell differentiation, involved in maternal-fetal immunotolerance. Interestingly, the protein expression of TSLP in normal pregnancy with significant TH2 bias is much higher than that of miscarriage showing TH1 bias at the maternal-fetal interface. Therefore, human trophoblasts may contribute to maternal-fetal tolerance by instructing dDCs to induce regulatory TH2 bias in human early pregnancy via TSLP.