Pilling Darrell, Consalvo Kristen M, Kirolos Sara A, Gomer Richard H
Department of Biology, Texas A&M University, College Station, TX 77843-3474 USA.
bioRxiv. 2025 May 12:2025.05.07.652701. doi: 10.1101/2025.05.07.652701.
Human males and females show differences in the incidence of neutrophil-associated diseases such as systemic lupus erythematosus, rheumatoid arthritis, and multiple sclerosis, and differences in neutrophil physiological responses such as responses to infection, tissue damage, and chemotactic factors. However, little is known about the basis of sex-based differences in human neutrophils.
Starting with human neutrophils from healthy donors, we used RNA-seq to examine total RNA profiles, RNAs not associated with ribosomes and thus not being translated, RNAs in monosomes, and RNAs in polysomes and thus heavily translated.
There were sex-based differences in the levels of RNAs across free RNA, monosome, and polysome fractions. Male neutrophils had increased levels of mRNAs encoding mitochondrial proteins in the free RNA fractions, indicating low levels of translation. The polysomes of male neutrophils were enriched for mRNAs encoding cytoskeletal organization, cell motility, and cell activation. The polysomes of female neutrophils were enriched for mRNAs associated the regulation of metabolic processes, cytokine responses, and mitochondrial proteins.
These data indicate that male and female neutrophils have different expression patterns and different translation efficiency of some mRNAs. This may contribute to the observed sex-based differences in neutrophil behavior and neutrophil-associated disease incidence and severity.
人类男性和女性在中性粒细胞相关疾病（如系统性红斑狼疮、类风湿性关节炎和多发性硬化症）的发病率上存在差异，在中性粒细胞对感染、组织损伤和趋化因子等生理反应方面也存在差异。然而，关于人类中性粒细胞中基于性别的差异的基础，我们知之甚少。
从健康供体的人类中性粒细胞开始，我们使用RNA测序来检查总RNA谱、不与核糖体相关因而不被翻译的RNA、单体中的RNA以及多聚体中的RNA（因此大量被翻译）。
在游离RNA、单体和多聚体部分的RNA水平上存在基于性别的差异。男性中性粒细胞在游离RNA部分中编码线粒体蛋白的mRNA水平增加，表明翻译水平较低。男性中性粒细胞的多聚体富含编码细胞骨架组织、细胞运动和细胞激活的mRNA。女性中性粒细胞的多聚体富含与代谢过程调节、细胞因子反应和线粒体蛋白相关的mRNA。
这些数据表明，男性和女性中性粒细胞具有不同的表达模式以及某些mRNA的不同翻译效率。这可能导致观察到的中性粒细胞行为以及中性粒细胞相关疾病发病率和严重程度方面基于性别的差异。
