性别差异在血液转录组中鉴定出与衰老和流感感染相关的免疫细胞比例的显著变化。
Sex Differences in the Blood Transcriptome Identify Robust Changes in Immune Cell Proportions with Aging and Influenza Infection.
机构信息
Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA; Program in Immunology, Stanford University School of Medicine, Stanford, CA, USA.
Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA 94305, USA.
出版信息
Cell Rep. 2019 Nov 12;29(7):1961-1973.e4. doi: 10.1016/j.celrep.2019.10.019.
Sex differences in autoimmunity and infection suggest that a better understanding of molecular sex differences will improve the diagnosis and treatment of immune-related disease. We identified 144 differentially expressed genes, referred to as immune sex expression signature (iSEXS), between human males and females using an integrated multi-cohort analysis of blood transcriptome profiles from six discovery cohorts from five continents with 458 healthy individuals. We validated iSEXS in 11 additional cohorts of 524 peripheral blood samples. When we separated iSEXS into genes located on sex chromosomes (XY-iSEXS) or autosomes (autosomal-iSEXS), both modules distinguished males and females. iSEXS reflects sex differences in immune cell proportions, with female-associated genes showing higher expression by CD4 T cells and male-associated genes showing higher expression by myeloid cells. Autosomal-iSEXS detected an increase in monocytes with age in females, reflected sex-differential immune cell dynamics during influenza infection, and predicted antibody response in males, but not females.
性别差异与自身免疫和感染有关，这表明更好地了解分子性别差异将有助于改善免疫相关疾病的诊断和治疗。我们使用来自五个大洲的六个发现队列的血液转录组谱的综合多队列分析，在男性和女性之间鉴定出 144 个差异表达基因，称为免疫性别表达特征 (iSEXS)，这些队列包含 458 名健康个体。我们在另外 11 个包含 524 个外周血样本的队列中验证了 iSEXS。当我们将 iSEXS 分为位于性染色体 (XY-iSEXS) 或常染色体 (autosomal-iSEXS) 上的基因时，两个模块都能区分男性和女性。iSEXS 反映了免疫细胞比例的性别差异，女性相关基因在 CD4 T 细胞中的表达更高，而男性相关基因在髓样细胞中的表达更高。常染色体 iSEXS 检测到女性单核细胞随年龄增长而增加，反映了流感感染期间免疫细胞动力学的性别差异，并预测了男性而非女性的抗体反应。
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