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.

The semiallogenic fetus is tolerated by the maternal immune system through control of innate and adaptive immune responses. Trophoblast cells secrete nanometer scale membranous particles called exosomes, which have been implicated in modulation of the local and systemic maternal immune system. Here we investigate the possibility that exosomes secreted from the first trimester and term placenta carry HLA-G and B7 family immunomodulators. Confocal microscopy of placental sections revealed intracellular co-localization of B7-H1 with CD63, suggesting that B7-H1 associates with subcellular vesicles that give rise to exosomes. First trimester and term placental explants were then cultured for 24 h. B7H-1 (CD274), B7-H3 (CD276) and HLA-G5 were abundant in pelleted supernatants of these cultures that contained microparticles and exosomes; the latter, however, was observed only in first trimester pellets and was nearly undetectable in term explant-derived pellets. Further purification of exosomes by sucrose density fractionation confirmed the association of these proteins specifically with exosomes. Finally, culture of purified trophoblast cells in the presence or absence of EGF suggested that despite the absence of HLA-G5 association with term explant-derived exosomes, it is present in exosomes secreted from mononuclear cytotrophoblast cells. Further, differentiation of cytotrophoblast cells reduced the presence of HLA-G5 in secreted exosomes. Together, the results suggest that the immunomodulatory proteins HLA-G5, B7-H1 and B7-H3, are secreted from early and term placenta, and have important implications in the mechanisms by which trophoblast immunomodulators modify the maternal immunological environment.

Skin is the first barrier of defense on fish, which is crucial to protection against different stressors, including pathogens. Skin samples obtained from dorsal and ventral part of Sparus aurata specimens were incubated with Photobacterium damselae subsp. piscicida (a pathogen for this fish species), with Shewanella putrefaciens Pdp11 (a probiotic bacteria isolated from healthy gilthead seabream skin) or with both bacteria. The gene expression profile of nine cytokines (il1b, tnfa, il6, il7, il8, il15, il18, il10 and tgfb) was studied by qPCR in all the skin samples. The present findings revealed different patterns of cytokine profile in dorsal and ventral skin of gilthead seabream, which could be related to the influence and susceptibility to a possible infection.