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A primate subfamily of galectins expressed at the maternal-fetal interface that promote immune cell death

Authors :
Than, Nandor Gabor
Romero, Roberto
Goodman, Morris
Weckle, Amy
Xing, Jun
Dong, Zhong
Xu, Yi
Tarquini, Federica
Szilagyi, Andras
Gal, Peter
Hou, Zhuocheng
Tarca, Adi L.
Kim, Chong Jai
Kim, Jung-Sun
Haidarian, Saied
Uddin, Monica
Bohn, Hans
Benirschke, Kurt
Santolaya-Forgas, Joaquin
Grossman, Lawrence I.
Erez, Offer
Hassan, Sonia S.
Zavodszky, Peter
Papp, Zoltan
Wildman, Derek E.
Source :
Proceedings of the National Academy of Sciences of the United States. June 16, 2009, Vol. 106 Issue 24, p9731, 6 p.
Publication Year :
2009

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. adaptive evolution | glycocode | maternal-fetal immune tolerance | PP13 | preeclampsia

Details

Language :
English
ISSN :
00278424
Volume :
106
Issue :
24
Database :
Gale General OneFile
Journal :
Proceedings of the National Academy of Sciences of the United States
Publication Type :
Academic Journal
Accession number :
edsgcl.203228013