Emergence of hormonal and redox regulation of galectin-1 in placental mammals: Implication in maternal-fetal immune tolerance

Nandor Gabor Than, Roberto Romero, Offer Erez, Amy Weckle, Adi L. Tarca, John Hotra, Asad Abbas, Mi Han Yu, Sung Su Kim, Juan Pedro Kusanovic, Francesca Gotsch, Zhuocheng Hou, Joaquin Santolaya-Forgas, Kurt Benirschke, Zoltan Papp, Lawrence I. Grossman, Morris Goodman, Derek E. Wildman

Research output: Contribution to journalArticlepeer-review

67 Scopus citations

Abstract

Galectin-1 is an anti-inflammatory lectin with pleiotropic regulatory functions at the crossroads of innate and adaptive immunity. It is expressed in immune privileged sites and is implicated in establishing maternal-fetal immune tolerance, which is essential for successful pregnancy in eutherian mammals. Here, we show conserved placental localization of galectin-1 in primates and its predominant expression in maternal decidua. Phylogenetic footprinting and shadowing unveil conserved cis motifs, including an estrogen responsive element in the 5′ promoter of LGALS1, that were gained during the emergence of placental mammals and could account for sex steroid regulation of LGALS1 expression, thus providing additional evidence for the role of galectin-1 in immune-endocrine cross-talk. Maximum parsimony and maximum likelihood analyses of 27 publicly available vertebrate and seven newly sequenced primate LGALS1 coding sequences reveal that intense purifying selection has been acting on residues in the carbohydrate recognition domain and dimerization interface that are involved in immune functions. Parsimony- and codon model-based phylogenetic analysis of coding sequences show that amino acid replacements occurred in early mammalian evolution on key residues, including gain of cysteines, which regulate immune functions by redox status-mediated conformational changes that disable sugar binding and dimerization, and that the acquired immunoregulatory functions of galectin-1 then became highly conserved in eutherian lineages, suggesting the emergence of hormonal and redox regulation of galectin-1 in placental mammals may be implicated in maternal-fetal immune tolerance.

Original languageEnglish
Pages (from-to)15819-15824
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number41
DOIs
StatePublished - 14 Oct 2008
Externally publishedYes

Keywords

  • Decidua
  • Estrogen
  • Glycocode
  • Immune-endocrine cross-talk
  • Pregnancy

ASJC Scopus subject areas

  • General

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