A pivotal role for galectin-1 in fetomaternal tolerance |
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Authors: | Blois Sandra M Ilarregui Juan M Tometten Mareike Garcia Mariana Orsal Arif S Cordo-Russo Rosalia Toscano Marta A Bianco Germán A Kobelt Peter Handjiski Bori Tirado Irene Markert Udo R Klapp Burghard F Poirier Francoise Szekeres-Bartho Julia Rabinovich Gabriel A Arck Petra C |
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Institution: | Charité, University Medicine Berlin, Biomedical Research Building, Campus Virchow, Augustenburger Platz 1, Berlin 13353, Germany. sandra.blois@charite.de |
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Abstract: | 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. |
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