Critical role of galectin-1 in fetomaternal tolerance.

BLOIS SM; ILARREGUI JM; GARCÍA MG; TOSCANO MA; BIANCO GA; RABINOVICH GA; ARCK PC

Río de Janeiro, Brasil.

Congreso; 13º Congreso Internacional de Inmunología; 2007

Blastocyst implantation and perpetuation of pregnancy requires a coordinated adaptation of the immune and endocrine system. Galectins can modulate the immune responses and a member of this protein family, galectin-1 (gal-1) is abundant in the female reproductive tract and placental tissue. We hypothesized that this immunoregulatory protein might play a pivotal role in regulating fetomaternal tolerance. In the present study we found that uterine Gal-1 expression is down-regulated in challenged murine pregnancies. Consistently, gal-1-/- mice exhibited increased rejection rates compared to wild-type mice even in undisturbed pregnancies (p<0.01). Treatment with recombinant Gal-1 prevented fetal rejections and restored multiple tolerance mechanisms including expansion of CD4+CD25+IL-10+ regulatory T cells in vivo (p<0.01), upregulation of Th2 cytokines (p<0.05), increased IDO expression and activation of negative inflammatory pathways; i.e TGF-��1 and Stat-3. In addition, galectin-1 promotes the generation of tolerogenic CD11c+ uterine DC with CD80/86lo and IL-10hi phenotype endowed with a regulatory function in the development of successful pregnancies. Finally, we provide evidence for a functional cross-talk between Gal-1 and the LH/progesterone axis in the maintenance of pregnancy. The present study demonstrates a novel role for Gal-1 as a pivotal and upstream messenger in the maintenance of fetomaternal tolerance and identifies a novel therapeutic target aiming at restoring immune tolerance in threatened pregnancies.-/- mice exhibited increased rejection rates compared to wild-type mice even in undisturbed pregnancies (p<0.01). Treatment with recombinant Gal-1 prevented fetal rejections and restored multiple tolerance mechanisms including expansion of CD4+CD25+IL-10+ regulatory T cells in vivo (p<0.01), upregulation of Th2 cytokines (p<0.05), increased IDO expression and activation of negative inflammatory pathways; i.e TGF-��1 and Stat-3. In addition, galectin-1 promotes the generation of tolerogenic CD11c+ uterine DC with CD80/86lo and IL-10hi phenotype endowed with a regulatory function in the development of successful pregnancies. Finally, we provide evidence for a functional cross-talk between Gal-1 and the LH/progesterone axis in the maintenance of pregnancy. The present study demonstrates a novel role for Gal-1 as a pivotal and upstream messenger in the maintenance of fetomaternal tolerance and identifies a novel therapeutic target aiming at restoring immune tolerance in threatened pregnancies.