It is well known that the estrogen receptor alpha gene (ESR1) affects the reproductive traits of pigs; however, the immune role of ESR1 gene has not yet been resolved. Here, we characterized the pleiotropic aspects of ESR1 gene in immunity using the pig model. Tissue expression profile showed that the ESR1 gene had a broad ectopic expression in multiple reproductive and immune-related tissues/organs, which provided the tissue-level spatial fundamental of ESR1 gene that might function as a pleiotropic immune regulator. Using the peripheral blood cell model, a coupling transcriptome analytical strategy was proposed and verified that there existed strong positive or negative correlations of ESR1 gene with hundreds of differentially expressed genes that were involved in the immune regulation, indicating that the ESR1 gene might affect or be affected by, directly or indirectly, dozens of immune-related genes in the peripheral blood cells. Furthermore, the results of genetic association analysis showed that the SmaI-polymorphism of ESR1 gene had significant or highly significant associations with multiple immune traits, including platelet (PLT), hematocrit (HCT), the number of CD4-CD8-CD3- cells, plateletcrit (PCT), mean corpuscular volume (MCV), and mean corpuscular hemoglobin concentration (MCHC). Multiple evidences supported the immune pleiotropic roles of ESR1 gene in pigs. The study advances our understanding of the cross-species immune pleiotropic landscape of ESR1 gene and also provides a potential pleiotropic molecular marker for disease-resistant breeding in pigs.

众所周知，雌激素受体α基因（ESR1）会影响猪的生​​殖特性。然而，ESR1基因的免疫作用尚未得到解决。在这里，我们使用猪模型表征了ESR1基因在免疫方面的多效性方面。组织表达谱显示，ESR1基因在多种生殖和免疫相关组织/器官中具有广泛的异位表达，这提供了ESR1基因在组织水平上的空间基础，可能起多效性免疫调节剂的作用。使用外周血细胞模型，提出了一种转录组分析策略，并验证了ESR1存在强正相关或负相关该基因具有数百个参与免疫调节的差异表达基因，表明ESR1基因可能直接或间接影响或受到外周血细胞中数十种免疫相关基因的影响。此外，遗传关联分析结果显示，ESR1基因的SmaI多态性与多种免疫性状（包括血小板（PLT），血细胞比容（HCT），CD4-CD8-CD3-细胞数量，血小板比容（PCT），平均红细胞体积（MCV）和平均红细胞血红蛋白浓度（MCHC）。多种证据支持ESR1的免疫多效性作用猪中的基因。该研究提高了我们对ESR1基因跨物种免疫多效性格局的了解，也为猪抗病育种提供了潜在的多效性分子标记。