Article abstract

Nature Medicine 13, 1450 - 1457 (2007)
Published online: 18 November 2007 | Corrected online: 7 May 2009 | doi:10.1038/nm1680



There is a Corrigendum (May 2009) associated with this Article.

A pivotal role for galectin-1 in fetomaternal tolerance

Sandra M Blois1, Juan M Ilarregui2,9, Mareike Tometten1,9, Mariana Garcia1, Arif S Orsal1, Rosalia Cordo-Russo1, Marta A Toscano2, Germán A Bianco2, Peter Kobelt3, Bori Handjiski1, Irene Tirado1,4, Udo R Markert5, Burghard F Klapp1, Francoise Poirier6, Julia Szekeres-Bartho7, Gabriel A Rabinovich2,8 & Petra C Arck1

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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  1. Charité, University Medicine Berlin, Biomedical Research Building, Campus Virchow, Augustenburger Platz 1, Berlin 13353, Germany.
  2. Laboratorio de Inmunopatología, Instituto de Biología y Medicina Experimental (IBYME), Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET), Vuelta de Obligado 2490, Buenos Aires C1428, Argentina.
  3. Department of Medicine, Division of Hepatology, Gastroenterology, and Endocrinology, Charité, University Medicine Berlin, Berlin 13353, Germany.
  4. Unidad de Inmunología, Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad de Granada, Granada 18012, Spain.
  5. Placenta-Labor, Department of Obstetrics, Friedrich-Schiller-University Jena, 07740 Jena, Germany.
  6. Departement de Biologie du Developpement, Institut Jacques Monod, Unités Mixtes de Recherche Centre National de la Recherche 7592, Univ. Paris 6 and Paris 7, Paris 75251 Paris, France.
  7. Department of Medical Microbiology and Immunology, Reproductive and Tumor Immunology Research Group of the Hungarian Academy of Sciences, Pecs University Medical School, Pecs 7643, Hungary.
  8. Departmento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires C1428, Argentina.
  9. J.M.I. and M.T. contributed equally to this work.

Correspondence to: Petra C Arck1 e-mail: petra.arck@charite.de

Correspondence to: Sandra M Blois1 e-mail: sandra.blois@charite.de

Correspondence to: Gabriel A Rabinovich2,8 e-mail: gabyrabi@ciudad.com.ar

* In the version of this article initially published, the plot labeled "Stress + Gal-1" duplicated the plot labeled "Control" for the IL-12p70 staining in Figure 2f. The corrected plots have now been provided in the HTML and PDF versions of the article. Two sentences were omitted from the section on purification of uterine DCs in the Methods. The sentences should have read: "We obtained purified DCs from uterine tissue in very low numbers. Thus, we pooled isolated cells from each group and used this cell cocktail for the isotype control staining." The error has been corrected in the HTML and PDF versions of the article. In Figure 4f, the lanes of the western blot were merged inappropriately. The properly presented blot, in which the gel lanes have been separated to indicate that the samples were not originally run side by side, has been provided in the PDF and HTML versions of the article. The standard curve of the cytometric bead array kit used to generate the cytokine data can be found in the revised supplementary information available online.

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