title: A primate subfamily of galectins expressed at the maternal-fetal interface that promote immune cell death.
abstract: Galectins are proteins that regulate immune responses through the recognition of cell-surface glycans. We present evidence that 16 human galectin genes are expressed at the maternal-fetal interface and demonstrate that a cluster of 5 galectin genes on human chromosome 19 emerged during primate evolution as a result of duplication and rearrangement of genes and pseudogenes via a birth and death process primarily mediated by transposable long interspersed nuclear elements (LINEs). Genes in the cluster are found only in anthropoids, a group of primate species that differ from their strepsirrhine counterparts by having relatively large brains and long gestations. Three of the human cluster genes (LGALS13, -14, and -16) were found to be placenta-specific. Homology modeling revealed conserved three-dimensional structures of galectins in the human cluster; however, analyses of 24 newly derived and 69 publicly available sequences in 10 anthropoid species indicate functional diversification by evidence of positive selection and amino acid replacements in carbohydrate-recognition domains. Moreover, we demonstrate altered sugar-binding capacities of 6 recombinant galectins in the cluster. We show that human placenta-specific galectins are predominantly expressed by the syncytiotrophoblast, a primary site of metabolic exchange where, early during pregnancy, the fetus comes in contact with immune cells circulating in maternal blood. Because ex vivo functional assays demonstrate that placenta-specific galectins induce the apoptosis of T lymphocytes, we propose that these galectins reduce the danger of maternal immune attacks on the fetal semiallograft, presumably conferring additional immune tolerance mechanisms and in turn sustaining hemochorial placentation during the long gestation of anthropoid primates.
authors.affiliation: Perinatology Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Detroit, MI 48201, USA.
authors.forename: Nandor Gabor
authors.initials: NG
authors.lastname: Than
authors.forename: Roberto
authors.initials: R
authors.lastname: Romero
authors.forename: Morris
authors.initials: M
authors.lastname: Goodman
authors.forename: Amy
authors.initials: A
authors.lastname: Weckle
authors.forename: Jun
authors.initials: J
authors.lastname: Xing
authors.forename: Zhong
authors.initials: Z
authors.lastname: Dong
authors.forename: Yi
authors.initials: Y
authors.lastname: Xu
authors.forename: Federica
authors.initials: F
authors.lastname: Tarquini
authors.forename: Andras
authors.initials: A
authors.lastname: Szilagyi
authors.forename: Peter
authors.initials: P
authors.lastname: Gal
authors.forename: Zhuocheng
authors.initials: Z
authors.lastname: Hou
authors.forename: Adi L
authors.initials: AL
authors.lastname: Tarca
authors.forename: Chong Jai
authors.initials: CJ
authors.lastname: Kim
authors.forename: Jung-Sun
authors.initials: JS
authors.lastname: Kim
authors.forename: Saied
authors.initials: S
authors.lastname: Haidarian
authors.forename: Monica
authors.initials: M
authors.lastname: Uddin
authors.forename: Hans
authors.initials: H
authors.lastname: Bohn
authors.forename: Kurt
authors.initials: K
authors.lastname: Benirschke
authors.forename: Joaquin
authors.initials: J
authors.lastname: Santolaya-Forgas
authors.forename: Lawrence I
authors.initials: LI
authors.lastname: Grossman
authors.forename: Offer
authors.initials: O
authors.lastname: Erez
authors.forename: Sonia S
authors.initials: SS
authors.lastname: Hassan
authors.forename: Peter
authors.initials: P
authors.lastname: Zavodszky
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Papp
authors.forename: Derek E
authors.initials: DE
authors.lastname: Wildman
mesh_terms: D000818:Animals; D016923:Cell Death / Q000235:genetics*; D002888:Chromosomes, Human, Pair 19; D005260:Female; D037161:Galectins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008431:Maternal-Fetal Exchange; D008958:Models, Molecular; D008969:Molecular Sequence Data; D005810:Multigene Family; D010802:Phylogeny; D011247:Pregnancy; D011323:Primates; D013601:T-Lymphocytes / Q000166:cytology*
chemical_list: D037161:Galectins