PNAS：胎儿免疫分子的早期起源 - 生物研究-生物谷

DerekWildman及其同事提出，这种类型的耐受是在哺乳动物发展的早期进化出的。这组科学家研究了一种称为galectin-1的抗炎症蛋白的结构，这种蛋白是在子宫等免疫反应受到抑制的“免疫赦免”区域发现的。在研究了来自包括几种灵长类动物在内的数种脊椎动物的该蛋白质后，这组作这发现了这种蛋白结构在有胎盘类哺乳动物的进化过程中是高度保守的。这组科学家提出，galectin-1结构的关键修改——这种修改可以让它执行其免疫功能——是在进化的早期出现的。相关论文发表在美国《国家科学院院刊》（ PNAS ）上。（生物谷Bioon.com）

生物谷推荐原始出处：

PNAS ，doi: 10.1073/pnas.0807606105，Nandor Gabor Than，Derek E. Wildman

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, AmyWeckle, Adi L. Tarca, John Hotra, Asad Abbas, Yu Mi Han, Sung-Su Kim,Juan Pedro Kusanovic, Francesca Gotsch, Zhuocheng Hou, JoaquinSantolaya-Forgas, Kurt Benirschke, Zoltan Papp, Lawrence I. Grossman,Morris Goodman, and Derek E. Wildman

Galectin-1is an anti-inflammatory lectin with pleiotropic regulatory functions atthe crossroads of innate and adaptive immunity. It is expressed inimmune privileged sites and is implicated in establishing maternal–fetalimmune tolerance, which is essential for successful pregnancy ineutherian mammals. Here, we show conserved placental localization ofgalectin-1 in primates and its predominant expression in maternaldecidua. 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 inimmune–endocrine cross-talk. Maximum parsimony and maximum likelihoodanalyses of 27 publicly available vertebrate and seven newly sequencedprimate LGALS1 codingsequences reveal that intense purifying selection has been acting onresidues in the carbohydrate recognition domain and dimerizationinterface that are involved in immune functions. Parsimony- and codonmodel-based phylogenetic analysis of coding sequences show that aminoacid replacements occurred in early mammalian evolution on key residues,including gain of cysteines, which regulate immune functions by redoxstatus-mediated conformational changes that disable sugar binding anddimerization, and that the acquired immunoregulatory functions ofgalectin-1 then became highly conserved in eutherian lineages,suggesting the emergence of hormonal and redox regulation of galectin-1in placental mammals may be implicated in maternal–fetal immunetolerance.