Immunomodulatory placental exosomes in pregnancy

Abstract

The placenta is an organ derived at embryogenesis from the trophectoderm and inner cell mass of the blastocyst. Several subpopulations of trophoblast cells, which originate from the trophectoderm, collectively give rise to a “trophoblast shell” that completely encases the fetus for the duration of pregnancy. As such, these cells form the anatomical interface between mother and fetus, and must arbitrate immunological responses of the mother to specific fetal antigens.Antigensexpressed in theplacenta include paternally-inherited as well as placenta-specific antigens; the latter includes at least one antigen, Trophoblast Glycoprotein (TPBG or 5T4) that can later appear as a tumor associated antigen. These antigens access the maternal lymphoid organs, as can be demonstrated immunohistologically, via a hematogenous route. Further, association of fetal/placental antigens with microvesicles and exosomes allows for immune modulation by trophoblast immune modulators co-expressed within these vesicles, which include inhibitory members of the B7 costimulatory family as well as HLA-G. Thus, the adaptive immune response to paternallyinherited and placenta-specific antigens is potently modified by placenta-derived vesicles. Supported by NIH grants HD049480 and HD045611.