A pivotal role for galectin-1 in fetomaternal tolerance

Sandra M. Blois, Juan M. Ilarregui, Mareike Tometten, Mariana Garcia, Arif S. Orsal, Rosalia Cordo-Russo, Marta A. Toscano, Germán A. Bianco, Peter Kobelt, Bori Handjiski, Irene Tirado, Udo R. Markert, Burghard F. Klapp, Francoise Poirier, Julia Szekeres-Bartho, Gabriel A. Rabinovich, Petra C. Arck

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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.

Original languageEnglish
Pages (from-to)1450-1457
Number of pages8
JournalNature medicine
Volume13
Issue number12
DOIs
Publication statusPublished - Dec 1 2007

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Blois, S. M., Ilarregui, J. M., Tometten, M., Garcia, M., Orsal, A. S., Cordo-Russo, R., Toscano, M. A., Bianco, G. A., Kobelt, P., Handjiski, B., Tirado, I., Markert, U. R., Klapp, B. F., Poirier, F., Szekeres-Bartho, J., Rabinovich, G. A., & Arck, P. C. (2007). A pivotal role for galectin-1 in fetomaternal tolerance. Nature medicine, 13(12), 1450-1457. https://doi.org/10.1038/nm1680