A PIVOTAL ROLE OF GALECTIN-1 IN FETOMATERNAL TOLERANCE

SANDRA M. BLOIS,; JUAN M. ILARREGUI,; MAREIKE TOMETTEN,; MARIANA GARCÍA,; ARIF SUPHI ORSAL,; ROSALIA CORDO-RUSSO,; MARTA A TOSCANO,; GERMÁN BIANCO,; BORI HANDJISKI,; IRENE TIRADO,; UDO R. MARKERT,; FRANCOISE POIRIER,; JULIA SZEKERES-BARTHO,; GABRIEL RABINOVICH*; PETRA C ARCK* (*PCA AND GAR COMPARTEN ULTIMA AUTORÍA Y CORRESPONDENCIA)

NATURE MEDICINE.

Nature Publishing Company

Lugar: New York; Año: 2007 vol. 13 p. 1450 - 1457

1078-8956

A successful pregnancy requires synchronized adaptation of maternal immune-endocrine mechanisms to the fetus. Here we show that galectin-1 (Gal-1), an immunoregulatory glycan-binding protein, has a pivotal role in conferring fetomaternal tolerance. Consistently with a marked decrease in Gal-1 expression during failing pregnancies, Gal-1-deficient (Lgals1-/-) mice showed higher rates of fetal loss compared to wild-type mice in allogeneic matings, whereas fetal survival was unaffected in syngeneic matings. Treatment with recombinant Gal-1 prevented fetal loss and restored tolerance through multiple mechanisms, including the induction of tolerogenic dendritic cells, which in turn promoted the expansion of interleukin-10 (IL-10)-secreting regulatory T cells in vivo. Accordingly, Gal-1´s protective effects were abrogated in mice depleted of regulatory T cells or deficient in IL-10. In addition, we provide evidence for synergy between Gal-1 and progesterone in the maintenance of pregnancy. Thus, Gal-1 is a pivotal regulator of fetomaternal tolerance that has potential therapeutic implications in threatened pregnancies.13(12):1450-7.