{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T14:49:53Z","timestamp":1787755793338,"version":"build-2784847793"},"reference-count":140,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,3,30]],"date-time":"2023-03-30T00:00:00Z","timestamp":1680134400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Epidemiological studies have revealed sex differences in the incidence and morbidity of respiratory virus infection in the human population, and often these observations are correlated with sex differences in the quality or magnitude of the immune response. Sex differences in immunity and morbidity also are observed in animal models of respiratory virus infection, suggesting differential dominance of specific immune mechanisms. Emerging research shows intrinsic sex differences in immune cell transcriptomes, epigenomes, and proteomes that may regulate human immunity when challenged by viral infection. Here, we highlight recent research into the role(s) of sex steroids and X chromosome complement in immune cells and describe how these findings provide insight into immunity during respiratory virus infection. We focus on the regulation of innate and adaptive immune cells by receptors for androgen and estrogens, as well as genes with a propensity to escape X chromosome inactivation. A deeper mechanistic knowledge of these pathways will help us to understand the often significant sex differences in immunity to endemic or pandemic respiratory pathogens such as influenza viruses, respiratory syncytial viruses and pathogenic coronaviruses.<\/jats:p>","DOI":"10.3389\/fphar.2023.1150282","type":"journal-article","created":{"date-parts":[[2023,3,30]],"date-time":"2023-03-30T04:42:26Z","timestamp":1680151346000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":17,"title":["Sex chromosome complement and sex steroid signaling underlie sex differences in immunity to respiratory virus infection"],"prefix":"10.3389","volume":"14","author":[{"given":"Reegan A. J.","family":"Miller","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abigael P.","family":"Williams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Kovats","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,3,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"77","DOI":"10.7150\/jgen.8123","article-title":"Chromosome imbalance as a driver of sex disparity in disease","volume":"2","author":"Abramowitz","year":"2014","journal-title":"J. Genomics"},{"key":"B2","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1038\/518288a","article-title":"Sex redefined","volume":"518","author":"Ainsworth","year":"2015","journal-title":"Nature"},{"key":"B3","doi-asserted-by":"publisher","first-page":"417","DOI":"10.2147\/IJGM.S67061","article-title":"The pattern of Middle East respiratory syndrome coronavirus in Saudi arabia: A descriptive epidemiological analysis of data from the Saudi ministry of health","volume":"7","author":"Alghamdi","year":"2014","journal-title":"Int. J. Gen. Med."},{"key":"B4","doi-asserted-by":"publisher","first-page":"e2223","DOI":"10.1002\/rmv.2223","article-title":"Sex-based differences in severity and mortality in COVID-19","volume":"31","author":"Alwani","year":"2021","journal-title":"Rev. Med. Virol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.yfrne.2008.11.001","article-title":"What does the \"four core genotypes\" mouse model tell us about sex differences in the brain and other tissues?","volume":"30","author":"Arnold","year":"2009","journal-title":"Front. Neuroendocrinol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1078","DOI":"10.1016\/j.cell.2015.08.021","article-title":"A distinct function of regulatory T cells in tissue protection","volume":"162","author":"Arpaia","year":"2015","journal-title":"Cell"},{"key":"B7","doi-asserted-by":"publisher","first-page":"229","DOI":"10.4049\/jimmunol.1602085","article-title":"IL-33-Responsive group 2 innate lymphoid cells are regulated by female sex hormones in the uterus","volume":"200","author":"Bartemes","year":"2018","journal-title":"J. Immunol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1016\/j.jaci.2021.04.029","article-title":"Targeting androgen signaling in ILC2s protects from IL-33-driven lung inflammation, independently of KLRG1","volume":"149","author":"Blanquart","year":"2022","journal-title":"J. Allergy Clin. Immunol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1151","DOI":"10.1111\/irv.13043","article-title":"Change in functional status associated with respiratory syncytial virus infection in hospitalized older adults","volume":"16","author":"Branche","year":"2022","journal-title":"Influenza Other Respir. Viruses"},{"key":"B10","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1186\/s12014-022-09371-z","article-title":"The dynamic changes and sex differences of 147 immune-related proteins during acute COVID-19 in 580 individuals","volume":"19","author":"Butler-Laporte","year":"2022","journal-title":"Clin. Proteomics"},{"key":"B11","doi-asserted-by":"publisher","first-page":"L272","DOI":"10.1152\/ajplung.00174.2007","article-title":"The impact of sex and sex hormones on lung physiology and disease: Lessons from animal studies","volume":"293","author":"Carey","year":"2007","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1182\/blood-2009-08-236935","article-title":"Estrogen receptor signaling promotes dendritic cell differentiation by increasing expression of the transcription factor IRF4","volume":"115","author":"Carreras","year":"2010","journal-title":"Blood"},{"key":"B13","doi-asserted-by":"publisher","first-page":"727","DOI":"10.4049\/jimmunol.180.2.727","article-title":"Estradiol acts directly on bone marrow myeloid progenitors to differentially regulate GM-CSF or Flt3 ligand-mediated dendritic cell differentiation","volume":"180","author":"Carreras","year":"2008","journal-title":"J. Immunol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"491","DOI":"10.3389\/fimmu.2020.00491","article-title":"Estrogen reverses HDAC inhibitor-mediated repression of Aicda and class-switching in antibody and autoantibody responses by downregulation of miR-26a","volume":"11","author":"Casali","year":"2020","journal-title":"Front. Immunol."},{"key":"B15","volume-title":"Estimated flu-related illnesses, medical visits, hospitalizations, and deaths in the United States - 2019-2020 flu season","year":"2021"},{"key":"B16","doi-asserted-by":"publisher","first-page":"2487","DOI":"10.1016\/j.celrep.2017.10.110","article-title":"Testosterone attenuates group 2 innate lymphoid cell-mediated airway inflammation","volume":"21","author":"Cephus","year":"2017","journal-title":"Cell Rep."},{"key":"B17","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1016\/j.chom.2016.01.007","article-title":"Dysregulated type I interferon and inflammatory monocyte-macrophage responses cause lethal pneumonia in SARS-CoV-infected mice","volume":"19","author":"Channappanavar","year":"2016","journal-title":"Cell Host Microbe"},{"key":"B18","doi-asserted-by":"publisher","first-page":"3625","DOI":"10.1172\/JCI126363","article-title":"IFN-I response timing relative to virus replication determines MERS coronavirus infection outcomes","volume":"129","author":"Channappanavar","year":"2019","journal-title":"J. Clin. Invest."},{"key":"B19","doi-asserted-by":"publisher","first-page":"4046","DOI":"10.4049\/jimmunol.1601896","article-title":"Sex-based differences in susceptibility to severe acute respiratory syndrome coronavirus infection","volume":"198","author":"Channappanavar","year":"2017","journal-title":"J. Immunol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"628","DOI":"10.1038\/s41584-020-0503-4","article-title":"Sex steroids and autoimmune rheumatic diseases: State of the art","volume":"16","author":"Cutolo","year":"2020","journal-title":"Nat. Rev. Rheumatol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1099","DOI":"10.15252\/emmm.201606413","article-title":"IFN\u03bb is a potent anti-influenza therapeutic without the inflammatory side effects of IFN\u03b1 treatment","volume":"8","author":"Davidson","year":"2016","journal-title":"EMBO Mol. Med."},{"key":"B22","doi-asserted-by":"publisher","first-page":"986","DOI":"10.1038\/ncomms1992","article-title":"FoxP3\u207a regulatory CD4 T cells control the generation of functional CD8 memory","volume":"3","author":"De Goer De Herve","year":"2012","journal-title":"Nat. Commun."},{"key":"B23","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1186\/s13052-020-0792-x","article-title":"Sex differences in blood pro-oxidant status and platelet activation in children admitted with respiratory syncytial virus bronchiolitis: A pilot study","volume":"46","author":"De Jacobis","year":"2020","journal-title":"Ital. J. Pediatr."},{"key":"B24","doi-asserted-by":"publisher","first-page":"e0097421","DOI":"10.1128\/mBio.00974-21","article-title":"Sex differences in lung imaging and SARS-CoV-2 antibody responses in a COVID-19 golden Syrian hamster model","volume":"12","author":"Dhakal","year":"2021","journal-title":"mBio"},{"key":"B25","doi-asserted-by":"publisher","first-page":"1529","DOI":"10.1126\/science.1093616","article-title":"Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA","volume":"303","author":"Diebold","year":"2004","journal-title":"Science"},{"key":"B26","doi-asserted-by":"publisher","first-page":"945762","DOI":"10.3389\/fimmu.2022.945762","article-title":"Sex bias in lymphocytes: Implications for autoimmune diseases","volume":"13","author":"Dodd","year":"2022","journal-title":"Front. Immunol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1084\/jem.20061839","article-title":"Peroxisome proliferator-activated receptor (PPAR)alpha expression in T cells mediates gender differences in development of T cell-mediated autoimmunity","volume":"204","author":"Dunn","year":"2007","journal-title":"J. Exp. Med."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1083","DOI":"10.4049\/jimmunol.2200294","article-title":"Androgens alleviate allergic airway inflammation by suppressing cytokine production in Th2 cells","volume":"209","author":"Ejima","year":"2022","journal-title":"J. Immunol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"e19409","DOI":"10.1371\/journal.pone.0019409","article-title":"Sex- and age-related differences in morbidity rates of 2009 pandemic influenza A H1N1 virus of swine origin in Japan","volume":"6","author":"Eshima","year":"2011","journal-title":"PLoS One"},{"key":"B30","doi-asserted-by":"publisher","first-page":"5565","DOI":"10.1038\/s41467-021-25828-5","article-title":"Polymorphic estrogen receptor binding site causes Cd2-dependent sex bias in the susceptibility to autoimmune diseases","volume":"12","author":"Fernandez Lahore","year":"2021","journal-title":"Nat. Commun."},{"key":"B31","doi-asserted-by":"publisher","first-page":"12477","DOI":"10.1073\/pnas.1805268115","article-title":"Biological sex affects vaccine efficacy and protection against influenza in mice","volume":"115","author":"Fink","year":"2018","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B32","doi-asserted-by":"publisher","first-page":"1777","DOI":"10.1038\/s41590-022-01329-5","article-title":"Pan-vaccine analysis reveals innate immune endotypes predictive of antibody responses to vaccination","volume":"23","author":"Fourati","year":"2022","journal-title":"Nat. Immunol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"869","DOI":"10.1073\/pnas.1321060111","article-title":"Systems analysis of sex differences reveals an immunosuppressive role for testosterone in the response to influenza vaccination","volume":"111","author":"Furman","year":"2014","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B34","doi-asserted-by":"publisher","first-page":"1843","DOI":"10.4049\/jimmunol.1800293","article-title":"Testosterone decreases house dust mite-induced type 2 and IL-17a-mediated airway inflammation","volume":"201","author":"Fuseini","year":"2018","journal-title":"J. Immunol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"e153397","DOI":"10.1172\/JCI153397","article-title":"Androgen receptor signaling promotes Treg suppressive function during allergic airway inflammation","volume":"132","author":"Gandhi","year":"2022","journal-title":"J. Clin. Invest."},{"key":"B36","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1186\/s13293-020-00304-9","article-title":"Impact of sex and gender on COVID-19 outcomes in Europe","volume":"11","author":"Gebhard","year":"2020","journal-title":"Biol. Sex. Differ."},{"key":"B37","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/j.jsbmb.2009.12.015","article-title":"Sex steroids as inflammatory regulators","volume":"120","author":"Gilliver","year":"2010","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1093\/infdis\/jiab422","article-title":"Sex differences in influenza: The challenge study experience","volume":"225","author":"Giurgea","year":"2022","journal-title":"J. Infect. Dis."},{"key":"B39","doi-asserted-by":"publisher","first-page":"646","DOI":"10.1089\/jwh.2020.8948","article-title":"Sex differences in COVID-19 hospitalization and mortality","volume":"30","author":"Gomez","year":"2021","journal-title":"J. Womens Health (Larchmt)"},{"key":"B40","doi-asserted-by":"publisher","first-page":"114288","DOI":"10.1016\/j.envres.2022.114288","article-title":"Sex-biased expression of the TLR7 gene in severe COVID-19 patients: Insights from transcriptomics and epigenomics","volume":"215","author":"Gomez-Carballa","year":"2022","journal-title":"Environ. Res."},{"key":"B41","doi-asserted-by":"publisher","first-page":"582214","DOI":"10.3389\/fimmu.2020.582214","article-title":"Estrogen receptor alpha signaling is responsible for the female sex bias in the loss of tolerance and immune cell activation induced by the lupus susceptibility locus Sle1b","volume":"11","author":"Graham","year":"2020","journal-title":"Front. Immunol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"5327","DOI":"10.4049\/jimmunol.1501684","article-title":"Sex differences in plasmacytoid dendritic cell levels of IRF5 drive higher IFN-alpha production in women","volume":"195","author":"Griesbeck","year":"2015","journal-title":"J. Immunol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"1886","DOI":"10.4049\/jimmunol.167.4.1886","article-title":"Cutting edge: Expansion and activation of a population of autoreactive marginal zone B cells in a model of estrogen-induced lupus","volume":"167","author":"Grimaldi","year":"2001","journal-title":"J. Immunol."},{"key":"B44","doi-asserted-by":"publisher","first-page":"791","DOI":"10.1038\/s41586-022-04522-6","article-title":"Androgen receptor activity in T cells limits checkpoint blockade efficacy","volume":"606","author":"Guan","year":"2022","journal-title":"Nature"},{"key":"B45","doi-asserted-by":"publisher","first-page":"2160","DOI":"10.3389\/fimmu.2019.02160","article-title":"Characterization of cxorf21 provides molecular insight into female-bias immune response in SLE pathogenesis","volume":"10","author":"Harris","year":"2019","journal-title":"Front. Immunol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"2373","DOI":"10.1093\/nar\/19.9.2373","article-title":"A frame-shift mutation in the androgen receptor gene causes complete androgen insensitivity in the testicular-feminized mouse","volume":"19","author":"He","year":"1991","journal-title":"Nucleic Acids Res."},{"key":"B47","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1038\/s41586-020-2282-0","article-title":"TASL is the SLC15A4-associated adaptor for IRF5 activation by TLR7-9","volume":"581","author":"Heinz","year":"2020","journal-title":"Nature"},{"key":"B48","doi-asserted-by":"publisher","first-page":"1091","DOI":"10.1038\/ni1008-1091","article-title":"The immunological genome Project: Networks of gene expression in immune cells","volume":"9","author":"Heng","year":"2008","journal-title":"Nat. Immunol."},{"key":"B49","doi-asserted-by":"publisher","first-page":"211","DOI":"10.2119\/molmed.2010.00172","article-title":"Differential roles of estrogen receptors alpha and beta in control of B-cell maturation and selection","volume":"17","author":"Hill","year":"2011","journal-title":"Mol. Med."},{"key":"B50","doi-asserted-by":"publisher","first-page":"6949","DOI":"10.1016\/j.vaccine.2015.08.044","article-title":"Sex differences in H7N9 influenza A virus pathogenesis","volume":"33","author":"Hoffmann","year":"2015","journal-title":"Vaccine"},{"key":"B51","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1038\/s41392-021-00709-x","article-title":"Multimodal single-cell omics analysis identifies epithelium-immune cell interactions and immune vulnerability associated with sex differences in COVID-19","volume":"6","author":"Hou","year":"2021","journal-title":"Signal Transduct. Target Ther."},{"key":"B52","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1007\/978-3-030-63046-1_7","article-title":"Roles of genetic predisposition in the sex bias of pulmonary pathophysiology, as a function of estrogens: Sex matters in the prevalence of lung diseases","volume":"1303","author":"Huang","year":"2021","journal-title":"Adv. Exp. Med. Biol."},{"key":"B53","doi-asserted-by":"publisher","first-page":"15131","DOI":"10.1073\/pnas.011513098","article-title":"Age and stage dependency of estrogen receptor expression by lymphocyte precursors","volume":"98","author":"Igarashi","year":"2001","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B54","doi-asserted-by":"publisher","first-page":"720952","DOI":"10.3389\/fimmu.2021.720952","article-title":"Sex differences in immunity to viral infections","volume":"12","author":"Jacobsen","year":"2021","journal-title":"Front. Immunol."},{"key":"B55","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1016\/s1074-7613(03)00208-5","article-title":"Plasmacytoid dendritic cells induce plasma cell differentiation through type I interferon and interleukin 6","volume":"19","author":"Jego","year":"2003","journal-title":"Immunity"},{"key":"B56","doi-asserted-by":"publisher","first-page":"e20211487","DOI":"10.1084\/jem.20211487","article-title":"The X in seX-biased immunity and autoimmune rheumatic disease","volume":"219","author":"Jiwrajka","year":"2022","journal-title":"J. Exp. Med."},{"key":"B57","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1530\/eje.0.1480111","article-title":"Altered circulating hormone levels, endothelial function and vascular reactivity in the testicular feminised mouse","volume":"148","author":"Jones","year":"2003","journal-title":"Eur. J. Endocrinol."},{"key":"B58","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1111\/imr.12706","article-title":"The group 2 innate lymphoid cell (ILC2) regulatory network and its underlying mechanisms","volume":"286","author":"Kabata","year":"2018","journal-title":"Immunol. Rev."},{"key":"B59","doi-asserted-by":"publisher","first-page":"74","DOI":"10.4049\/immunohorizons.1800008","article-title":"A major population of functional KLRG1(-) ILC2s in female lungs contributes to a sex bias in ILC2 numbers","volume":"2","author":"Kadel","year":"2018","journal-title":"Immunohorizons"},{"key":"B60","doi-asserted-by":"publisher","first-page":"1653","DOI":"10.3389\/fimmu.2018.01653","article-title":"Sex hormones regulate innate immune cells and promote sex differences in respiratory virus infection","volume":"9","author":"Kadel","year":"2018","journal-title":"Front. Immunol."},{"key":"B61","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1093\/aje\/kwh056","article-title":"Do men have a higher case fatality rate of severe acute respiratory syndrome than women do?","volume":"159","author":"Karlberg","year":"2004","journal-title":"Am. J. Epidemiol."},{"key":"B62","doi-asserted-by":"publisher","first-page":"720090","DOI":"10.3389\/fimmu.2021.720090","article-title":"The immunological factors predisposing to severe covid-19 are already present in healthy elderly and men","volume":"12","author":"Kilic","year":"2021","journal-title":"Front. Immunol."},{"key":"B63","doi-asserted-by":"publisher","first-page":"9887","DOI":"10.1073\/pnas.1402468111","article-title":"Androgens alter T-cell immunity by inhibiting T-helper 1 differentiation","volume":"111","author":"Kissick","year":"2014","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B64","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1189\/jlb.0811427","article-title":"Mechanisms of sex disparities in influenza pathogenesis","volume":"92","author":"Klein","year":"2012","journal-title":"J. Leukoc. Biol."},{"key":"B65","doi-asserted-by":"publisher","first-page":"5591","DOI":"10.1172\/JCI133935","article-title":"BCG vaccination in humans inhibits systemic inflammation in a sex-dependent manner","volume":"130","author":"Koeken","year":"2020","journal-title":"J. Clin. Invest."},{"key":"B66","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/j.cellimm.2015.01.018","article-title":"Estrogen receptors regulate innate immune cells and signaling pathways","volume":"294","author":"Kovats","year":"2015","journal-title":"Cell Immunol."},{"key":"B67","doi-asserted-by":"publisher","first-page":"1872","DOI":"10.1001\/jama.2009.1496","article-title":"Critically ill patients with 2009 influenza A(H1N1) infection in Canada","volume":"302","author":"Kumar","year":"2009","journal-title":"JAMA"},{"key":"B68","doi-asserted-by":"publisher","first-page":"eabq2630","DOI":"10.1126\/sciimmunol.abq2630","article-title":"Androgen conspires with the CD8(+) T cell exhaustion program and contributes to sex bias in cancer","volume":"7","author":"Kwon","year":"2022","journal-title":"Sci. Immunol."},{"key":"B69","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1677\/joe.1.06264","article-title":"Is dehydroepiandrosterone a hormone?","volume":"187","author":"Labrie","year":"2005","journal-title":"J. Endocrinol."},{"key":"B70","doi-asserted-by":"publisher","first-page":"1581","DOI":"10.1084\/jem.20161807","article-title":"Androgen signaling negatively controls group 2 innate lymphoid cells","volume":"214","author":"Laffont","year":"2017","journal-title":"J. Exp. Med."},{"key":"B71","doi-asserted-by":"publisher","first-page":"5444","DOI":"10.4049\/jimmunol.1303400","article-title":"X-Chromosome complement and estrogen receptor signaling independently contribute to the enhanced TLR7-mediated IFN-alpha production of plasmacytoid dendritic cells from women","volume":"193","author":"Laffont","year":"2014","journal-title":"J. Immunol."},{"key":"B72","doi-asserted-by":"publisher","first-page":"351","DOI":"10.4049\/jimmunol.1801208","article-title":"The multifaceted B cell response to influenza virus","volume":"202","author":"Lam","year":"2019","journal-title":"J. Immunol."},{"key":"B73","doi-asserted-by":"publisher","first-page":"1125","DOI":"10.1165\/rcmb.2010-0516OC","article-title":"Infection with influenza virus induces IL-33 in murine lungs","volume":"45","author":"Le Goffic","year":"2011","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"B74","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1038\/nri.2016.95","article-title":"Interleukin-33 in health and disease","volume":"16","author":"Liew","year":"2016","journal-title":"Nat. Rev. Immunol."},{"key":"B75","doi-asserted-by":"publisher","first-page":"e28482","DOI":"10.7554\/eLife.28482","article-title":"A comprehensive analysis of coregulator recruitment, androgen receptor function and gene expression in prostate cancer","volume":"6","author":"Liu","year":"2017","journal-title":"Elife"},{"key":"B76","doi-asserted-by":"publisher","first-page":"9246","DOI":"10.1016\/j.vaccine.2011.09.110","article-title":"Antibody responses and cross protection against lethal influenza A viruses differ between the sexes in C57BL\/6 mice","volume":"29","author":"Lorenzo","year":"2011","journal-title":"Vaccine"},{"key":"B77","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41574-022-00780-6","article-title":"Sex hormones in SARS-CoV-2 susceptibility: Key players or confounders?","author":"Lott","year":"2022","journal-title":"Nat. Rev. Endocrinol."},{"key":"B78","doi-asserted-by":"publisher","first-page":"37797","DOI":"10.1074\/jbc.M110.169086","article-title":"Estrogen receptors bind to and activate the HOXC4\/HoxC4 promoter to potentiate HoxC4-mediated activation-induced cytosine deaminase induction, immunoglobulin class switch DNA recombination, and somatic hypermutation","volume":"285","author":"Mai","year":"2010","journal-title":"J. Biol. Chem."},{"key":"B79","doi-asserted-by":"publisher","first-page":"969","DOI":"10.1038\/s41385-019-0171-3","article-title":"Sex-associated TSLP-induced immune alterations following early-life RSV infection leads to enhanced allergic disease","volume":"12","author":"Malinczak","year":"2019","journal-title":"Mucosal Immunol."},{"key":"B80","doi-asserted-by":"publisher","first-page":"1691","DOI":"10.3390\/cancers3021691","article-title":"Epigenetics of estrogen receptor signaling: Role in hormonal cancer progression and therapy","volume":"3","author":"Mann","year":"2011","journal-title":"Cancers (Basel)"},{"key":"B81","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1038\/s41467-020-14396-9","article-title":"Sexual-dimorphism in human immune system aging","volume":"11","author":"Marquez","year":"2020","journal-title":"Nat. Commun."},{"key":"B82","doi-asserted-by":"publisher","first-page":"e0214286","DOI":"10.1371\/journal.pone.0214286","article-title":"Female and male mouse lung group 2 innate lymphoid cells differ in gene expression profiles and cytokine production","volume":"14","author":"Matha","year":"2019","journal-title":"PLoS One"},{"key":"B83","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1016\/j.immuni.2022.04.013","article-title":"Mucosal immune responses to infection and vaccination in the respiratory tract","volume":"55","author":"Mettelman","year":"2022","journal-title":"Immunity"},{"key":"B84","doi-asserted-by":"publisher","first-page":"eaap9415","DOI":"10.1126\/scisignal.aap9415","article-title":"Estrogen receptor alpha contributes to T cell-mediated autoimmune inflammation by promoting T cell activation and proliferation","volume":"11","author":"Mohammad","year":"2018","journal-title":"Sci. Signal"},{"key":"B85","doi-asserted-by":"publisher","first-page":"1045","DOI":"10.1031\/ni.2131","article-title":"Innate lymphoid cells promote lung-tissue homeostasis after infection with influenza virus","volume":"12","author":"Monticelli","year":"2011","journal-title":"Nat. Immunol."},{"key":"B86","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1016\/s0092-8674(00)00078-7","article-title":"Class switch recombination and hypermutation require activation-induced cytidine deaminase (AID), a potential RNA editing enzyme","volume":"102","author":"Muramatsu","year":"2000","journal-title":"Cell"},{"key":"B87","doi-asserted-by":"publisher","first-page":"2164","DOI":"10.1038\/s41467-019-10106-2","article-title":"Interferon inducible X-linked gene CXorf21 may contribute to sexual dimorphism in Systemic Lupus Erythematosus","volume":"10","author":"Odhams","year":"2019","journal-title":"Nat. Commun."},{"key":"B88","doi-asserted-by":"publisher","first-page":"789","DOI":"10.4049\/jimmunol.1800931","article-title":"Cutting edge: CXCR3 escapes X chromosome inactivation in T cells during infection: Potential implications for sex differences in immune responses","volume":"203","author":"Oghumu","year":"2019","journal-title":"J. Immunol."},{"key":"B89","doi-asserted-by":"publisher","first-page":"625833","DOI":"10.3389\/fimmu.2020.625833","article-title":"Signaling through nucleic acid sensors and their roles in inflammatory diseases","volume":"11","author":"Okude","year":"2020","journal-title":"Front. Immunol."},{"key":"B90","doi-asserted-by":"publisher","first-page":"65","DOI":"10.32598\/jpr.8.2.65","article-title":"A systematic review and meta-analysis of sex differences in morbidity and mortality of acute lower respiratory tract infections among african children","volume":"8","author":"Orimadegun","year":"2020","journal-title":"J. Pediatr. Rev."},{"key":"B91","doi-asserted-by":"publisher","first-page":"540","DOI":"10.1038\/ni.1725","article-title":"HoxC4 binds to the promoter of the cytidine deaminase AID gene to induce AID expression, class-switch DNA recombination and somatic hypermutation","volume":"10","author":"Park","year":"2009","journal-title":"Nat. Immunol."},{"key":"B92","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/j.imlet.2004.10.007","article-title":"Differential estrogen receptor gene expression in human peripheral blood mononuclear cell populations","volume":"97","author":"Phiel","year":"2005","journal-title":"Immunol. Lett."},{"key":"B93","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1210\/er.2015-1034","article-title":"Determinants of receptor- and tissue-specific actions in androgen signaling","volume":"36","author":"Pihlajamaa","year":"2015","journal-title":"Endocr. Rev."},{"key":"B94","doi-asserted-by":"publisher","first-page":"2227","DOI":"10.4049\/jimmunol.173.4.2227","article-title":"Cutting edge: Estrogen drives expansion of the CD4+CD25+ regulatory T cell compartment","volume":"173","author":"Polanczyk","year":"2004","journal-title":"J. Immunol."},{"key":"B95","doi-asserted-by":"publisher","first-page":"626107","DOI":"10.3389\/fphar.2021.626107","article-title":"Interplay between endocrine disruptors and immunity: Implications for diseases of autoreactive etiology","volume":"12","author":"Popescu","year":"2021","journal-title":"Front. Pharmacol."},{"key":"B96","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1038\/s41541-019-0124-6","article-title":"Age-associated changes in the impact of sex steroids on influenza vaccine responses in males and females","volume":"4","author":"Potluri","year":"2019","journal-title":"NPJ Vaccines"},{"key":"B97","doi-asserted-by":"publisher","first-page":"986840","DOI":"10.3389\/fimmu.2022.986840","article-title":"Consequences of sex differences in Type I IFN responses for the regulation of antiviral immunity","volume":"13","author":"Pujantell","year":"2022","journal-title":"Front. Immunol."},{"key":"B98","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1210\/jcem.87.1.8265","article-title":"Editorial: The postnatal gonadotropin and sex steroid surge-insights from the androgen insensitivity syndrome","volume":"87","author":"Quigley","year":"2002","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"B99","doi-asserted-by":"publisher","first-page":"23741","DOI":"10.1038\/s41598-021-03044-x","article-title":"Sex differences in innate anti-viral immune responses to respiratory viruses and in their clinical outcomes in a birth cohort study","volume":"11","author":"Regis","year":"2021","journal-title":"Sci. Rep."},{"key":"B100","doi-asserted-by":"publisher","first-page":"5838","DOI":"10.1016\/j.cell.2021.10.023","article-title":"COVID-19 immune features revealed by a large-scale single-cell transcriptome atlas","volume":"184","author":"Ren","year":"2021","journal-title":"Cell"},{"key":"B101","doi-asserted-by":"publisher","first-page":"84","DOI":"10.6065\/apem.2040094.047","article-title":"Minipuberty of human infancy - a window of opportunity to evaluate hypogonadism and differences of sex development?","volume":"25","author":"Renault","year":"2020","journal-title":"Ann. Pediatr. Endocrinol. Metab."},{"key":"B102","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1186\/2042-6410-2-8","article-title":"Sex chromosome complement contributes to sex differences in coxsackievirus B3 but not influenza A virus pathogenesis","volume":"2","author":"Robinson","year":"","journal-title":"Biol. Sex. Differ."},{"key":"B103","doi-asserted-by":"publisher","first-page":"e1002149","DOI":"10.1371\/journal.ppat.1002149","article-title":"Elevated 17\u03b2-estradiol protects females from influenza A virus pathogenesis by suppressing inflammatory responses","volume":"7","author":"Robinson","year":"","journal-title":"PLoS Pathog."},{"key":"B104","doi-asserted-by":"publisher","first-page":"e710","DOI":"10.1016\/S2665-9913(22)00198-9","article-title":"Investigating sex differences in T regulatory cells from cisgender and transgender healthy individuals and patients with autoimmune inflammatory disease: A cross-sectional study","volume":"4","author":"Robinson","year":"2022","journal-title":"Lancet Rheumatol."},{"key":"B105","doi-asserted-by":"publisher","first-page":"e12776","DOI":"10.1111\/sji.12776","article-title":"Copy number of the X-linked genes TLR7 and CD40L influences innate and adaptive immune responses","volume":"90","author":"Sarmiento","year":"2019","journal-title":"Scand. J. Immunol."},{"key":"B106","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1016\/j.pharmthera.2015.01.007","article-title":"Sex steroid signaling: Implications for lung diseases","volume":"150","author":"Sathish","year":"2015","journal-title":"Pharmacol. Ther."},{"key":"B107","doi-asserted-by":"publisher","first-page":"924","DOI":"10.1016\/j.cels.2022.10.005","article-title":"Pre-infection antiviral innate immunity contributes to sex differences in SARS-CoV-2 infection","volume":"13","author":"Sauerwald","year":"2022","journal-title":"Cell Syst."},{"key":"B108","doi-asserted-by":"publisher","first-page":"51","DOI":"10.3389\/fimmu.2012.00051","article-title":"Molecular mechanisms of treg-mediated T cell suppression","volume":"3","author":"Schmidt","year":"2012","journal-title":"Front. Immunol."},{"key":"B109","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1016\/j.coviro.2011.10.008","article-title":"Interferon-stimulated genes and their antiviral effector functions","volume":"1","author":"Schoggins","year":"2011","journal-title":"Curr. Opin. Virol."},{"key":"B110","doi-asserted-by":"publisher","first-page":"ofab448","DOI":"10.1093\/ofid\/ofab448","article-title":"Sex and gender differences in testing, hospital admission, clinical presentation, and drivers of severe outcomes from COVID-19","volume":"8","author":"Scully","year":"2021","journal-title":"Open Forum Infect. Dis."},{"key":"B111","doi-asserted-by":"publisher","first-page":"454","DOI":"10.1182\/blood-2011-08-371831","article-title":"The TLR-mediated response of plasmacytoid dendritic cells is positively regulated by estradiol in vivo through cell-intrinsic estrogen receptor alpha signaling","volume":"119","author":"Seillet","year":"2012","journal-title":"Blood"},{"key":"B112","doi-asserted-by":"publisher","first-page":"861","DOI":"10.1016\/j.cell.2021.01.007","article-title":"Adaptive immunity to SARS-CoV-2 and COVID-19","volume":"184","author":"Sette","year":"2021","journal-title":"Cell"},{"key":"B113","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/s8756-3282(01)00643-3","article-title":"Deletion of estrogen receptors reveals a regulatory role for estrogen receptors-beta in bone remodeling in females but not in males","volume":"30","author":"Sims","year":"2002","journal-title":"Bone"},{"key":"B114","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1186\/s13072-015-0035-3","article-title":"Characterization of whole-genome autosomal differences of DNA methylation between men and women","volume":"8","author":"Singmann","year":"2015","journal-title":"Epigen. Chromatin"},{"key":"B115","doi-asserted-by":"publisher","first-page":"eaap8855","DOI":"10.1126\/sciimmunol.aap8855","article-title":"TLR7 escapes X chromosome inactivation in immune cells","volume":"3","author":"Souyris","year":"2018","journal-title":"Sci. Immunol."},{"key":"B116","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1007\/s00281-018-0712-y","article-title":"Female predisposition to TLR7-driven autoimmunity: Gene dosage and the escape from X chromosome inactivation","volume":"41","author":"Souyris","year":"2019","journal-title":"Semin. Immunopathol."},{"key":"B117","doi-asserted-by":"publisher","first-page":"1619","DOI":"10.1016\/j.cell.2022.04.012","article-title":"Precision medicine requires understanding how both sex and gender influence health","volume":"185","author":"Stachenfeld","year":"2022","journal-title":"Cell"},{"key":"B118","doi-asserted-by":"publisher","first-page":"919","DOI":"10.1002\/JLB.6RI0319-094R","article-title":"When the balance is broken: X-Linked gene dosage from two X chromosomes and female-biased autoimmunity","volume":"106","author":"Syrett","year":"2019","journal-title":"J. Leukoc. Biol."},{"key":"B119","doi-asserted-by":"publisher","first-page":"456","DOI":"10.1002\/jcp.21221","article-title":"Induction of regulatory T cells by physiological level estrogen","volume":"214","author":"Tai","year":"2008","journal-title":"J. Cell Physiol."},{"key":"B120","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1038\/s41586-020-2700-3","article-title":"Sex differences in immune responses that underlie COVID-19 disease outcomes","volume":"588","author":"Takahashi","year":"2020","journal-title":"Nature"},{"key":"B121","doi-asserted-by":"publisher","first-page":"1111","DOI":"10.1016\/j.cell.2016.10.018","article-title":"Host and environmental factors influencing individual human cytokine responses","volume":"167","author":"Ter Horst","year":"2016","journal-title":"Cell"},{"key":"B122","doi-asserted-by":"publisher","first-page":"697","DOI":"10.3389\/fimmu.2020.00697","article-title":"Testosterone protects against severe influenza by reducing the pro-inflammatory cytokine response in the murine lung","volume":"11","author":"Tuku","year":"2020","journal-title":"Front. Immunol."},{"key":"B123","doi-asserted-by":"publisher","first-page":"e0183922","DOI":"10.1128\/mbio.01839-22","article-title":"Greater breadth of vaccine-induced immunity in females than males is mediated by increased antibody diversity in germinal center B cells","volume":"13","author":"Ursin","year":"2022","journal-title":"mBio"},{"key":"B124","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1146\/annurev-virology-091919-092720","article-title":"Sex differences in respiratory viral pathogenesis and treatments","volume":"8","author":"Ursin","year":"2021","journal-title":"Annu. Rev. Virol."},{"key":"B125","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1038\/s41586-020-2040-3","article-title":"Sex-specific adipose tissue imprinting of regulatory T cells","volume":"579","author":"Vasanthakumar","year":"2020","journal-title":"Nature"},{"key":"B126","doi-asserted-by":"publisher","first-page":"3306","DOI":"10.1210\/en.2018-00486","article-title":"Estriol reduces pulmonary immune cell recruitment and inflammation to protect female mice from severe influenza","volume":"159","author":"Vermillion","year":"","journal-title":"Endocrinology"},{"key":"B127","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1186\/s13293-018-0184-8","article-title":"Production of amphiregulin and recovery from influenza is greater in males than females","volume":"9","author":"Vermillion","year":"","journal-title":"Biol. Sex. Differ."},{"key":"B128","doi-asserted-by":"publisher","first-page":"e13085","DOI":"10.1111\/irv.13085","article-title":"The burden of non-SARS-CoV2 viral lower respiratory tract infections in hospitalized children in barcelona (Spain): A long-term, clinical, epidemiologic and economic study","volume":"17","author":"Vila","year":"2022","journal-title":"Influenza Other Respir. Viruses"},{"key":"B129","doi-asserted-by":"publisher","first-page":"180","DOI":"10.3389\/fimmu.2019.00180","article-title":"Sex differences in older adults' immune responses to seasonal influenza vaccination","volume":"10","author":"Voigt","year":"2019","journal-title":"Front. Immunol."},{"key":"B130","doi-asserted-by":"publisher","first-page":"103988","DOI":"10.1016\/j.cellimm.2019.103988","article-title":"Testosterone treatment of aged male mice improves some but not all aspects of age-associated increases in influenza severity","volume":"345","author":"Vom Steeg","year":"2019","journal-title":"Cell Immunol."},{"key":"B131","doi-asserted-by":"publisher","first-page":"e1008506","DOI":"10.1371\/journal.ppat.1008506","article-title":"Androgen receptor signaling in the lungs mitigates inflammation and improves the outcome of influenza in mice","volume":"16","author":"Vom Steeg","year":"2020","journal-title":"PLoS Pathog."},{"key":"B132","doi-asserted-by":"publisher","first-page":"L1234","DOI":"10.1152\/ajplung.00352.2016","article-title":"Age and testosterone mediate influenza pathogenesis in male mice","volume":"311","author":"Vom Steeg","year":"2016","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"B133","doi-asserted-by":"publisher","first-page":"E2029","DOI":"10.1073\/pnas.1520113113","article-title":"Unusual maintenance of X chromosome inactivation predisposes female lymphocytes for increased expression from the inactive X","volume":"113","author":"Wang","year":"2016","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B134","doi-asserted-by":"publisher","first-page":"3167","DOI":"10.3389\/fimmu.2018.03167","article-title":"Sex and pubertal differences in the type 1 interferon pathway associate with both X chromosome number and serum sex hormone concentration","volume":"9","author":"Webb","year":"2018","journal-title":"Front. Immunol."},{"key":"B135","volume-title":"Sex, gender and influenza","author":"Who","year":"2010"},{"key":"B136","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1146\/annurev-immunol-101320-125133","article-title":"Sex differences in immunity","volume":"40","author":"Wilkinson","year":"2022","journal-title":"Annu. Rev. Immunol."},{"key":"B137","doi-asserted-by":"publisher","first-page":"e133251","DOI":"10.1172\/jci.insight.133251","article-title":"Estradiol resolves pneumonia via ER\u03b2 in regulatory T cells","volume":"6","author":"Xiong","year":"2021","journal-title":"JCI Insight"},{"key":"B138","doi-asserted-by":"publisher","first-page":"755","DOI":"10.1016\/j.medj.2021.04.008","article-title":"Mucosal-associated invariant T cell responses differ by sex in COVID-19","volume":"2","author":"Yu","year":"2021","journal-title":"Med. (N Y)"},{"key":"B139","doi-asserted-by":"publisher","first-page":"9505","DOI":"10.1073\/pnas.1118458109","article-title":"Peroxisome proliferator-activated receptor (PPAR)\u03b1 and -\u03b3 regulate IFN\u03b3 and IL-17A production by human T cells in a sex-specific way","volume":"109","author":"Zhang","year":"2012","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B140","doi-asserted-by":"publisher","DOI":"10.1042\/bsr20202074","article-title":"Sex differences in immune responses to SARS-CoV-2 in patients with COVID-19","volume":"41","author":"Zhao","year":"2021","journal-title":"Biosci. Rep."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2023.1150282\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,30]],"date-time":"2023-03-30T04:42:30Z","timestamp":1680151350000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2023.1150282\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,30]]},"references-count":140,"alternative-id":["10.3389\/fphar.2023.1150282"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2023.1150282","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,30]]},"article-number":"1150282"}}