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    Biological sex significantly impacts human immune function, influencing disease susceptibility and treatment responses. Systems immunology reveals how sex chromosomes and hormones shape immunity, enabling sex-specific medical interventions.

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    Area of Science:

    • Immunology
    • Systems Biology
    • Human Genetics

    Background:

    • Human immune function exhibits significant variability, with biological sex being a primary determinant.
    • Men often experience more severe infections and higher cancer incidence, whereas women show enhanced vaccine responses but greater autoimmunity prevalence.
    • Intrinsic sex differences stem from chromosomal sex and sex hormone signaling pathways affecting various cell types.

    Purpose of the Study:

    • To analyze the current literature on immune sex differences in humans using systems immunology approaches.
    • To elucidate the mechanisms by which biological sex modulates human immunity, focusing on sex chromosomes and hormones.
    • To explore how systems immunology advances the understanding of sex-based immune variations in health and disease.

    Main Methods:

    • Literature analysis of systems immunology applications in studying human immune sex differences.
    • Examination of mechanisms including sex chromosomes, sex hormones, cell composition, transcriptomics, epigenomics, metabolomics, spatial and cell-cell interactions, and plasma proteomics.
    • Review of systems-level applications for investigating sex differences in immune responses to perturbations.

    Main Results:

    • Biological sex, influenced by chromosomes and hormones, profoundly impacts immune cell composition, gene expression, and metabolic profiles.
    • Systems immunology reveals sex-specific differences in immune system states and responses to challenges.
    • Sex differences are evident across multiple molecular and cellular levels, from epigenomics to cell interactions.

    Conclusions:

    • Systems immunology offers a powerful framework for decoding sex-regulated immune pathways.
    • Understanding these sex differences is crucial for developing precise, sex-informed therapeutic strategies.
    • This approach paves the way for tailored interventions addressing sex disparities in immune-related conditions.