ImmGen report: sexual dimorphism in the immune system transcriptome

• Published in: Nature communications Vol. 10; no. 1; pp. 4295 - 14
• Main Authors: Gal-Oz, Shani Talia, Maier, Barbara, Yoshida, Hideyuki, Seddu, Kumba, Elbaz, Nitzan, Czysz, Charles, Zuk, Or, Stranger, Barbara E., Ner-Gaon, Hadas, Shay, Tal
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 20.09.2019; Nature Publishing Group; Nature Portfolio
• Subjects: 38/91; 45/23; 49/31; 49/39; 49/90; 631/114; 631/250/2502/2170; 631/250/2502/248; 631/250/2504/342; 64; 64/60; Animals; Autoimmune diseases; Computational Biology; Epigenomics; Female; Females; Gender aspects; Gender differences; Gene expression; Gene Expression Profiling; Gene Expression Regulation; Genes; Genomics; Humanities and Social Sciences; Humans; Immune response; Immune System; Immunity, Innate - genetics; Infectious diseases; Interferon; Interferons - metabolism; Macrophages; Male; Males; Mice; Mice, Inbred C57BL; Monocytes; multidisciplinary; Nucleotide sequence; Ribonucleic acid; RNA; Science; Science (multidisciplinary); Sex Characteristics; Sex differences; Sex Factors; Sexual dimorphism; Transcription; Transcriptome
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-019-12348-6

Sexual dimorphism in the mammalian immune system is manifested as more frequent and severe infectious diseases in males and, on the other hand, higher rates of autoimmune disease in females, yet insights underlying those differences are still lacking. Here we characterize sex differences in the immune system by RNA and ATAC sequence profiling of untreated and interferon-induced immune cell types in male and female mice. We detect very few differentially expressed genes between male and female immune cells except in macrophages from three different tissues. Accordingly, very few genomic regions display differences in accessibility between sexes. Transcriptional sexual dimorphism in macrophages is mediated by genes of innate immune pathways, and increases after interferon stimulation. Thus, the stronger immune response of females may be due to more activated innate immune pathways prior to pathogen invasion. Sexual dimorphism is observed frequently in immune disorders, but the underlying insights are still unclear. Here the authors analyze transcriptome and epigenome changes induced by interferon in various mouse immune cell types, and find only a restricted set of sexual dimorphism genes in innate immunity and macrophages.