A pivotal role for galectin-1 in fetomaternal tolerance.
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.
Blois
Sandra M
SM
Charité, University Medicine Berlin, Biomedical Research Building, Campus Virchow, Augustenburger Platz 1, Berlin 13353, Germany. sandra.blois@charite.de
Ilarregui
Juan M
JM
Tometten
Mareike
M
Garcia
Mariana
M
Orsal
Arif S
AS
Cordo-Russo
Rosalia
R
Toscano
Marta A
MA
Bianco
Germán A
GA
Kobelt
Peter
P
Handjiski
Bori
B
Tirado
Irene
I
Markert
Udo R
UR
Klapp
Burghard F
BF
Poirier
Francoise
F
Szekeres-Bartho
Julia
J
Rabinovich
Gabriel A
GA
Arck
Petra C
PC
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
D037483:Galectin 1; D053645:Interleukin-2 Receptor alpha Subunit; D011134:Polysaccharides