A pivotal role for galectin-1 in fetomaternal tolerance
Standard
A pivotal role for galectin-1 in fetomaternal tolerance. / Blois, Sandra M; Ilarregui, Juan M; Tometten, Mareike; Garcia, Mariana; Orsal, Arif S; Cordo-Russo, Rosalia; Toscano, Marta A; Bianco, Germán A; Kobelt, Peter; Handjiski, Bori; Tirado, Irene; Markert, Udo R; Klapp, Burghard F; Poirier, Francoise; Szekeres-Bartho, Julia; Rabinovich, Gabriel A; Arck, Petra C.
in: NAT MED, Jahrgang 13, Nr. 12, 12.2007, S. 1450-7.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - A pivotal role for galectin-1 in fetomaternal tolerance
AU - Blois, Sandra M
AU - Ilarregui, Juan M
AU - Tometten, Mareike
AU - Garcia, Mariana
AU - Orsal, Arif S
AU - Cordo-Russo, Rosalia
AU - Toscano, Marta A
AU - Bianco, Germán A
AU - Kobelt, Peter
AU - Handjiski, Bori
AU - Tirado, Irene
AU - Markert, Udo R
AU - Klapp, Burghard F
AU - Poirier, Francoise
AU - Szekeres-Bartho, Julia
AU - Rabinovich, Gabriel A
AU - Arck, Petra C
PY - 2007/12
Y1 - 2007/12
N2 - 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.
AB - 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.
KW - Animals
KW - CD4-Positive T-Lymphocytes/metabolism
KW - Female
KW - Galectin 1/genetics
KW - Gene Expression Regulation, Developmental
KW - Histocompatibility, Maternal-Fetal
KW - Immune Tolerance
KW - Interleukin-2 Receptor alpha Subunit/biosynthesis
KW - Mice
KW - Mice, Transgenic
KW - Polysaccharides/chemistry
KW - Pregnancy
KW - Pregnancy, Animal
KW - T-Lymphocytes, Regulatory/metabolism
KW - Transplantation, Homologous
U2 - 10.1038/nm1680
DO - 10.1038/nm1680
M3 - SCORING: Journal article
C2 - 18026113
VL - 13
SP - 1450
EP - 1457
JO - NAT MED
JF - NAT MED
SN - 1078-8956
IS - 12
ER -