A CRITICAL ROLE FOR GALECTIN-1 IN THE MAINTENANCE OF MATERNAL-FETAL TOLERANCE.

BLOIS SM; ILARREGUI JM; GARCIA MG; ORSAL AS; TOSCANO M; RABINOVICH G; ARK PC

Córdoba, Argentina

Congreso; VII Latin American Congress of Immunology; 2005

Asociación Latinoamericana de Inmunología

Galectin (Gal-1), one of the earliest identified members of a family of lectins, occurs in a variety of tissues undergoing dramatic changes, e.g. the feto-placental unit. An intriguing function of Gal-1 is its modulation of immune responses. Thus, Gal-1 is likely a key modulator of pregnancy maintenance. Uterine Gal-1 expression was evaluated in uterine tissue from normal, failing and progesterone-rescued  murine pregnancies by immunohistochemistry. Additionally, mice failing pregnancies triggered by stress exposure were treated recombinant Gal-1. Phenotype and maturity of dendritic cells (DC) as well as tolerance mechanisms at the feto-maternal interface were also evaluated in the respective groups by flow cytometry and ELISA. The immunomodulatory effects of DCs on allogeneic mixed-lymphocytes responses upon Gal-1 treatment were also tested in vitro. Uterine expression of Gal-1 is down-regulated in failing pregnancies and restored by progesterone. Treatment with Gal1 prevents fetal rejection by increasing the presence an uterine Gal-1bright  DC population. Subsequently, Gal-1bright  DC mediate fetal tolerance via a Th2 skew, prevention of Th1 cells, up-regulation of indoleamine 2, 3 dioxygenase and CD4+CD25brigth T regulatory cells and synthesis of asymmetric antibodies. Our data provide clear evidence for the modulatory function of gal-1 in pregnancy maintenance and suggest Gal-1 as promising therapeutic novel agent to improve reproductive outcome.