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Sex Differences in the Blood Transcriptome Identify Robust Changes in Immune Cell Proportions with Aging and Influenza Infection

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  • Sex Differences in the Blood Transcriptome Identify Robust Changes in Immune Cell Proportions with Aging and Influenza Infection


    Cell Rep. 2019 Nov 12;29(7):1961-1973.e4. doi: 10.1016/j.celrep.2019.10.019. Sex Differences in the Blood Transcriptome Identify Robust Changes in Immune Cell Proportions with Aging and Influenza Infection.

    Bongen E1, Lucian H2, Khatri A2, Fragiadakis GK3, Bjornson ZB3, Nolan GP3, Utz PJ4, Khatri P5.
    Author information

    1 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. 2 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. 3 Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA; Baxter Laboratory for Stem Cell Biology, Stanford University School of Medicine, Stanford, CA 94305, USA. 4 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. Electronic address: pjutz@stanford.edu. 5 Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Medicine, Division of Biomedical Informatics Research, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: pkhatri@stanford.edu.

    Abstract

    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.
    Copyright ? 2019 The Authors. Published by Elsevier Inc. All rights reserved.


    KEYWORDS:

    CD4(+) T cells; aging; immune system; immunology; influenza; meta-analysis; monocytes; multi-cohort analysis; sex differences; transcriptome

    PMID: 31722210 DOI: 10.1016/j.celrep.2019.10.019

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