Decoding sex differences in human immunity through systems immunology.

Oxford open immunology Pub Date : 2025-07-04 eCollection Date: 2025-01-01 DOI:10.1093/oxfimm/iqaf006
Joan Escrivà-Font, Tianze Cao, Camila Rosat Consiglio
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Abstract

Immune function varies widely across humans. Biological sex is a key factor underlying human immune variability, with men presenting with more severe infections and increased cancer rates, while women exhibit higher vaccine responses and prevalence of autoimmunity. Intrinsic biological sex differences arise from varying contributions of chromosomal sex, and sex hormone sensing and downstream signaling to different cell types. This complex regulation presents a unique opportunity for the exploration of human immune sex differences using systems-level methods of investigation. Here we analyze the current literature and the applications of systems immunology in elucidating the immune sex differences in humans. We examine mechanisms of biological sex modulation of human immunity via sex chromosomes, and particularly emphasize the role of sex hormones. We then focus on how systems immunology has been advancing our understanding of how sex impacts the healthy immune system at steady state, ranging from cell composition, transcriptomics, epigenomics, metabolomics, spatial and cell-cell interactions, to plasma proteomics. We also examine systems-level applications to investigating sex differences upon immune perturbations and give an overview of key future directions for the field. Systems immunology provides a powerful framework to decode biological sex-regulated pathways in immunity, paving the way for more precise, sex-informed therapeutic interventions to address sex differences in immune-related conditions.

通过系统免疫学解读人体免疫的性别差异。
人类的免疫功能差异很大。生理性别是人类免疫变异的一个关键因素,男性表现出更严重的感染和更高的癌症发病率,而女性表现出更高的疫苗反应和自身免疫的患病率。生物学上的内在性别差异源于染色体性别、性激素感知和下游信号对不同细胞类型的不同贡献。这种复杂的调节提供了一个独特的机会,探索人类免疫性别差异使用系统级的调查方法。在此,我们分析了目前的文献和系统免疫学在阐明人类免疫性别差异方面的应用。我们研究了通过性染色体对人类免疫的生物性别调节机制,并特别强调性激素的作用。然后,我们关注系统免疫学如何推进我们对性别如何影响健康免疫系统稳态的理解,范围从细胞组成、转录组学、表观基因组学、代谢组学、空间和细胞-细胞相互作用到血浆蛋白质组学。我们还研究了系统级应用,以调查免疫扰动时的性别差异,并概述了该领域未来的关键方向。系统免疫学提供了一个强大的框架来解码免疫中的生物性别调节途径,为更精确、性别知情的治疗干预铺平了道路,以解决免疫相关疾病的性别差异。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
2.20
自引率
0.00%
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审稿时长
9 weeks
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