INVESTIGADORES
TOSCANO Marta Alicia
artículos
Título:
Galectin-1 confers immune privilege to human trophoblast: implications in recurrent fetal loss
Autor/es:
RAMHORST RE; GIRIBALDI L; FRACCAROLI L; TOSCANO MA; STUPIRSKI JC; ROMERO MD; DURAND ES; RUBINSTEIN N; BLASCHITZ A; SEDLMAYR P; GENTI-RAIMONDI S; FAINBOIM L; RABINOVICH GA
Revista:
GLYCOBIOLOGY
Editorial:
OXFORD UNIV PRESS INC
Referencias:
Lugar: Oxford; Año: 2012 vol. 22 p. 1374 - 1386
ISSN:
0959-6658
Resumen:
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 (Treg)
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.