title: Galectin-1 confers immune privilege to human trophoblast: implications in recurrent fetal loss.
abstract: Mechanisms accounting for the protection of the fetal semi-allograft from maternal immune cells remain incompletely understood. In previous studies, we showed that galectin-1 (Gal1), an immunoregulatory glycan-binding protein, hierarchically triggers a cascade of tolerogenic events at the mouse fetomaternal interface. Here, we show that Gal1 confers immune privilege to human trophoblast cells through the modulation of a number of regulatory mechanisms. Gal1 was mainly expressed in invasive extravillous trophoblast cells of human first trimester and term placenta in direct contact with maternal tissue. Expression of Gal1 by the human trophoblast cell line JEG-3 was primarily controlled by progesterone and pro-inflammatory cytokines and impaired T-cell responses by limiting T cell viability, suppressing the secretion of Th1-type cytokines and favoring the expansion of CD4(+)CD25(+)FoxP3(+) regulatory T (T(reg)) cells. Targeted inhibition of Gal1 expression through antibody (Ab)-mediated blockade, addition of the specific disaccharide lactose or retroviral-mediated siRNA strategies prevented these immunoregulatory effects. Consistent with a homeostatic role of endogenous Gal1, patients with recurrent pregnancy loss showed considerably lower levels of circulating Gal1 and had higher frequency of anti-Gal1 auto-Abs in their sera compared with fertile women. Thus, endogenous Gal1 confers immune privilege to human trophoblast cells by triggering a broad tolerogenic program with potential implications in threatened pregnancies.
authors: Laboratory of Immunopharmacology, Department of Biological Chemistry, Faculty of Exact and Natural Sciences, University of Buenos Aires, Argentina.
authors: Rosanna E
authors: RE
authors: Ramhorst
authors: Laura
authors: L
authors: Giribaldi
authors: Laura
authors: L
authors: Fraccaroli
authors: Marta A
authors: MA
authors: Toscano
authors: Juan C
authors: JC
authors: Stupirski
authors: Marta D
authors: MD
authors: Romero
authors: Edith S
authors: ES
authors: Durand
authors: Natalia
authors: N
authors: Rubinstein
authors: Astrid
authors: A
authors: Blaschitz
authors: Peter
authors: P
authors: Sedlmayr
authors: Susana
authors: S
authors: Genti-Raimondi
authors: Leonardo
authors: L
authors: Fainboim
authors: Gabriel A
authors: GA
authors: Rabinovich
mesh_terms: D000026:Abortion, Habitual / Q000276:immunology*; D002460:Cell Line; D002470:Cell Survival / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D037483:Galectin 1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000276:immunology*; D006801:Humans; D011374:Progesterone / Q000494:pharmacology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D014327:Trophoblasts / Q000166:cytology / Q000276:immunology*
chemical_list: D016207:Cytokines; D037483:Galectin 1; D011374:Progesterone