title: A pivotal role for galectin-1 in fetomaternal tolerance.
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.
authors.affiliation: Charité, University Medicine Berlin, Biomedical Research Building, Campus Virchow, Augustenburger Platz 1, Berlin 13353, Germany. sandra.blois@charite.de
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Blois
authors.forename: Juan M
authors.initials: JM
authors.lastname: Ilarregui
authors.forename: Mareike
authors.initials: M
authors.lastname: Tometten
authors.forename: Mariana
authors.initials: M
authors.lastname: Garcia
authors.forename: Arif S
authors.initials: AS
authors.lastname: Orsal
authors.forename: Rosalia
authors.initials: R
authors.lastname: Cordo-Russo
authors.forename: Marta A
authors.initials: MA
authors.lastname: Toscano
authors.forename: Germán A
authors.initials: GA
authors.lastname: Bianco
authors.forename: Peter
authors.initials: P
authors.lastname: Kobelt
authors.forename: Bori
authors.initials: B
authors.lastname: Handjiski
authors.forename: Irene
authors.initials: I
authors.lastname: Tirado
authors.forename: Udo R
authors.initials: UR
authors.lastname: Markert
authors.forename: Burghard F
authors.initials: BF
authors.lastname: Klapp
authors.forename: Francoise
authors.initials: F
authors.lastname: Poirier
authors.forename: Julia
authors.initials: J
authors.lastname: Szekeres-Bartho
authors.forename: Gabriel A
authors.initials: GA
authors.lastname: Rabinovich
authors.forename: Petra C
authors.initials: PC
authors.lastname: Arck
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D005260:Female; D037483:Galectin 1 / Q000235:genetics / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D054502:Histocompatibility, Maternal-Fetal; D007108:Immune Tolerance; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis; D051379:Mice; D008822:Mice, Transgenic; D011134:Polysaccharides / Q000737:chemistry; D011247:Pregnancy; D011270:Pregnancy, Animal; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism; D014184:Transplantation, Homologous
chemical_list: D037483:Galectin 1; D053645:Interleukin-2 Receptor alpha Subunit; D011134:Polysaccharides