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

Blood. 2010 Sep 23;116(12):2061-9. doi: 10.1182/blood-2009-11-252940. Epub 2010 Jun 10.

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 T(H)2-attracting chemokine CCL-17. The TSLP-activated dDCs prime decidual CD4(+) T cells for T(H)2 cell differentiation, involved in maternal-fetal immunotolerance. Interestingly, the protein expression of TSLP in normal pregnancy with significant T(H)2 bias is much higher than that of miscarriage showing T(H)1 bias at the maternal-fetal interface. Therefore, human trophoblasts may contribute to maternal-fetal tolerance by instructing dDCs to induce regulatory T(H)2 bias in human early pregnancy via TSLP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cytokines / genetics
  • Cytokines / immunology*
  • Cytokines / metabolism
  • Decidua / immunology
  • Dendritic Cells / immunology*
  • Female
  • Fetus / immunology
  • Humans
  • Immune Tolerance
  • Pregnancy / immunology
  • RNA, Messenger / analysis
  • Solubility
  • Th2 Cells / immunology*
  • Thymic Stromal Lymphopoietin
  • Trophoblasts / immunology
  • Trophoblasts / metabolism*

Substances

  • Cytokines
  • RNA, Messenger
  • Thymic Stromal Lymphopoietin