Artículo
Galectin-1 confers immune privilege to human trophoblast: Implications in recurrent fetal loss
Ramhorst, Rosanna Elizabeth
; Giribaldi, María Laura
; Fraccaroli, Laura Virginia
; Toscano, Marta Alicia
; Stupirski, Juan Carlos
; Romero, Marta D.; Durand, Edith Sandra
; Rubinstein, Natalia
; Blaschitz, Astrid; Sedlmayr, Peter; Genti de Raimondi, Susana
; Fainboim, Leonardo
; Rabinovich, Gabriel Adrián
Fecha de publicación:
10/2012
Editorial:
Oxford Univ Press Inc
Revista:
Glycobiology
ISSN:
0959-6658
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Mechanisms accounting for protection of the fetal semiallograft from maternal immune cells remain incompletely understood. In previous studies we showed that galectin-1 (Gal1), an immunoregulatory glycan-binding protein, plays key roles in modulating immune responses during murine pregnancies. Here we show that Gal1 fosters immune privilege at the human fetomaternal interface through modulation of multiple tolerance mechanisms. Gal1 was mainly expressed in invasive extravillous trophoblast cells of human first trimester and term placenta in direct contact with maternal tissue. Trophoblast-derived Gal1 was primarily controlled by progesterone and pro-inflammatory cytokines and fostered T cell tolerance by favoring the expansion of CD4+CD25+FoxP3+ regulatory T (Treg) cells, suppressing the secretion of Th1-type cytokines and limiting T cell viability. Targeted inhibition of Gal1 expression through different strategies including Ab-mediated blockade, addition of the specific disaccharide lactose and silencing through retroviral-mediated siRNA strategies prevented these immunoregulatory effects. Consistent with a tolerogenic function for endogenous Gal1, patients with recurrent pregnancy loss showed considerably lower levels of circulating Gal1 and had greatly enhanced frequency of anti-Gal1 autoantibodies in their sera compared with fertile women. Thus, endogenous Gal1 confers immune privilege to human trophoblasts by triggering a broad tolerogenic program, with potential implications in threatened pregnancies.
Palabras clave:
Fetal Loss
,
Fetomaternal Tolerance
,
Galectin-1
,
Pregnancy
,
Progesterone
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Articulos(IFIBYNE)
Articulos de INST.DE FISIOL., BIOL.MOLECULAR Y NEUROCIENCIAS
Articulos de INST.DE FISIOL., BIOL.MOLECULAR Y NEUROCIENCIAS
Citación
Ramhorst, Rosanna Elizabeth; Giribaldi, María Laura; Fraccaroli, Laura Virginia; Toscano, Marta Alicia; Stupirski, Juan Carlos; et al.; Galectin-1 confers immune privilege to human trophoblast: Implications in recurrent fetal loss; Oxford Univ Press Inc; Glycobiology; 22; 10; 10-2012; 1374-1386
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