Sexual dimorphism in the immune system is evidenced by a higher prevalence of autoimmune diseases in women and higher susceptibility to infectious diseases in men. However, the molecular basis of these sex-based differences is not fully understood. We have characterized the transcriptome profiles of peripheral blood monocytes from males and postmenopausal females with chronic low-grade inflammation. We identified 41 sexually differentially expressed genes [adjusted p value (FDR) < 0.1], including genes involved in immune cell activation (e.g., CEACAM1, FCGR2B, and SLAMF7) and antigen presentation (e.g., AIM2, CD1E, and UBA1) with a higher expression in females than males. Moreover, signaling pathways of immune or inflammatory responses, including interferon (IFN) signaling [z-score = 2.45, -log(p) = 3.88], were found to be more upregulated in female versus male monocytes, based on a set of genes exhibiting sex-biased expression (p < 0.03). The contribution of IFN signaling to the sexual transcriptional differences was further confirmed by direct comparisons of the monocyte sex-biased genes with IFN signature genes (ISGs) that were previously curated in mouse macrophages. ISGs showed a greater overlap with female-biased genes than male-biased genes and a higher overall expression in female than male monocytes, particularly for the genes of antiviral and inflammatory responses to IFN. Given the role of IFN in immune defense and autoimmunity, our results suggest that sexual dimorphism in immune functions may be associated with more priming of innate immune pathways in female than male monocytes. These findings highlight the role of sex on the human immune transcriptome.

中文翻译：

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慢性低度炎症个体单核细胞转录组的性别二态性


免疫系统中的性别二态性表现为女性自身免疫性疾病的患病率较高，而男性对传染病的易感性较高。然而，这些性别差异的分子基础尚未完全了解。我们对患有慢性低度炎症的男性和绝经后女性的外周血单核细胞的转录组谱进行了表征。我们鉴定了 41 个性别差异表达基因 [调整后的 p 值 (FDR) < 0.1]，包括参与免疫细胞激活（例如 CEACAM1、FCGR2B 和 SLAMF7）和抗原呈递（例如 AIM2、CD1E 和 UBA1）的基因女性中的表达量高于男性。此外，基于一组基因，免疫或炎症反应的信号通路，包括干扰素 (IFN) 信号通路 [z 得分 = 2.45，-log(p) = 3.88]，被发现在女性单核细胞中比男性单核细胞上调更多表现出性别偏见的表达（p％3C 0.03）。通过将单核细胞性别偏向基因与先前在小鼠巨噬细胞中策划的 IFN 特征基因 (ISG) 进行直接比较，进一步证实了 IFN 信号传导对性别转录差异的贡献。 ISGs 与偏向女性的基因比偏向男性的基因有更大的重叠，并且在女性单核细胞中的总体表达高于男性单核细胞，特别是对于 IFN 的抗病毒和炎症反应基因。鉴于干扰素在免疫防御和自身免疫中的作用，我们的结果表明，免疫功能的性别二态性可能与女性单核细胞比男性单核细胞更多地启动先天免疫途径有关。这些发现强调了性别对人类免疫转录组的作用。