A pivotal role for galectin-1 in fetomaternal tolerance

被引:386
作者
Blois, Sandra M.
Ilarregui, Juan M.
Tometten, Mareike
Garcia, Mariana
Orsal, Arif S.
Cordo-Russo, Rosalia
Toscano, Marta A.
Bianco, German A.
Kobelt, Peter
Handjiski, Bori
Tirado, Irene
Markert, Udo R.
Klapp, Burghard F.
Poirier, Francoise
Szekeres-Bartho, Julia
Rabinovich, Gabriel A.
Arck, Petra C.
机构
[1] Univ Med Berlin, Charite, Biomed Res Bldg, D-13353 Berlin, Germany
[2] Consejo Nacl Invest Cient & Tecn, Inst Biol & Med Expt, Immunopathol Lab, RA-1428 Buenos Aires, DF, Argentina
[3] Univ Med Berlin, Charite, Dept Med, Div Hepatol Gastroenterol & Endocrinol, D-13353 Berlin, Germany
[4] Univ Granada, Fac Med, Dept Bioquim & Biol Mol, Unidad Immunol, E-18012 Granada, Spain
[5] Univ Jena, Dept Obstet, Placenta Labor, D-07740 Jena, Germany
[6] Univ Paris 06, Inst Jacques Monod, Ctr Natl Rech, Dept Biol & Dev,UMR 7592, F-75251 Paris, France
[7] Univ Paris 07, F-75221 Paris 05, France
[8] Univ Pecs, Sch Med, Hungarian Acad Sci, Dept Med Microbiol & Immunol,Reprod & Tumor Immun, H-7643 Pecs, Hungary
[9] Univ Buenos Aires, Fac Ciencias Exactas & Nat, Dept Quim Biol, RA-1428 Buenos Aires, DF, Argentina
关键词
D O I
10.1038/nm1680
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:1450 / 1457
页数:8
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