A critical role for galectin-1 in the maintenance of maternal-fetal tolerance

BLOIS SANDRA MARÍA, ILARREGUI JUAN MARTÍN, GARCÍA MARIANA GABRIELA, ORSAL ARIF SUPHL, TOSCANO MARTA, RABINOVICH GABRIEL ADRIÁN, ARCK PETRA CLARA

Córdoba, Argentina

Congreso; VII Latin American Congress of Immunology; 2005

Latin Ameircan Society of Immunology

A CRITICAL ROLE FOR GALECTIN-1 IN THE MAINTENANCE OF MATERNAL-FETAL TOLERANCE SM Blois 1, JM Ilarregui 2, MG Garcia1, AS Örsal 1, GA Rabinovich 2 & PC Arck 1.       1 Charité, University Medicine Berlin, Berlin, Germany.   2 Division of Immunogenetics, Hospital Clínicas “José de San Martín”, Buenos Aires, Argentina.     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 modulators of pregnancy maintenance. Uterine Gal-1 expression was evaluated in uterine tissue from normal, failing and progesterone-rescued murine pregnancies by immunohistochemistry. Additionally, mice with failing pregnancies triggered by stress exposure were treated with 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-lymphocyte 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 gal-1 prevents fetal rejection by increasing the presence of 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+CD25bright 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 a promising therapeutic novel agent to improve reproductive outcome.