Emergence of hormonal and redox regulation of galectin-1 in placental mammals: implication in maternal-fetal immune tolerance.
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.
Than
Nandor Gabor
NG
Perinatology Research Branch, National Institute of Child Health and Human Development, National Institutes of Health, and Department of Health and Human Services, Detroit, MI 48201, USA.
Romero
Roberto
R
Erez
Offer
O
Weckle
Amy
A
Tarca
Adi L
AL
Hotra
John
J
Abbas
Asad
A
Han
Yu Mi
YM
Kim
Sung-Su
SS
Kusanovic
Juan Pedro
JP
Gotsch
Francesca
F
Hou
Zhuocheng
Z
Santolaya-Forgas
Joaquin
J
Benirschke
Kurt
K
Papp
Zoltan
Z
Grossman
Lawrence I
LI
Goodman
Morris
M
Wildman
Derek E
DE
D000818:Animals; D005075:Biological Evolution; D019295:Computational Biology; D030561:Databases, Nucleic Acid; D005260:Female; D037483:Galectin 1 / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000276:immunology / Q000502:physiology*; D012739:Gonadal Steroid Hormones / Q000502:physiology*; D007108:Immune Tolerance; D008431:Maternal-Fetal Exchange / Q000276:immunology; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D010802:Phylogeny; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011323:Primates; D014714:Vertebrates
D037483:Galectin 1; D012739:Gonadal Steroid Hormones