{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T02:57:38Z","timestamp":1785898658204,"version":"3.56.0"},"reference-count":140,"publisher":"Frontiers Media SA","funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["1 R01 GM118602"],"award-info":[{"award-number":["1 R01 GM118602"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"DOI":"10.3389\/fimmu.2017.01455","type":"journal-article","created":{"date-parts":[[2017,11,13]],"date-time":"2017-11-13T08:41:01Z","timestamp":1510562461000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":58,"title":["Inherent X-Linked Genetic Variability and Cellular Mosaicism Unique to Females Contribute to Sex-Related Differences in the Innate Immune Response"],"prefix":"10.3389","volume":"8","author":[{"given":"Zoltan","family":"Spolarics","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geber","family":"Pe\u00f1a","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Qin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"Donnelly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David H.","family":"Livingston","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2017,11,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1007\/BF03324754","article-title":"Men: good health and high mortality. Sex differences in health and aging","volume":"20","author":"Oksuzyan","year":"2008","journal-title":"Aging Clin Exp Res"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1711","DOI":"10.1042\/CS20160004","article-title":"Gender, aging and longevity in humans: an update of an intriguing\/neglected scenario paving the way to a gender-specific medicine","volume":"130","author":"Ostan","year":"2016","journal-title":"Clin Sci (Lond)"},{"key":"B3","doi-asserted-by":"publisher","first-page":"626","DOI":"10.1038\/nri.2016.90","article-title":"Sex differences in immune responses","volume":"16","author":"Klein","year":"2016","journal-title":"Nat Rev Immunol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"2187","DOI":"10.1172\/JCI78082","article-title":"Sexual dimorphism in autoimmunity","volume":"125","author":"Rubtsova","year":"2015","journal-title":"J Clin Invest"},{"key":"B5","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.jaut.2009.03.007","article-title":"The genetics and epigenetics of autoimmune diseases","volume":"33","author":"Hewagama","year":"2009","journal-title":"J Autoimmun"},{"key":"B6","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.jaut.2009.03.005","article-title":"Female predominance and X chromosome defects in autoimmune diseases","volume":"33","author":"Invernizzi","year":"2009","journal-title":"J Autoimmun"},{"key":"B7","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1097\/00024382-200014020-00001","article-title":"Effect of gender and sex hormones on immune responses following shock","volume":"14","author":"Angele","year":"2000","journal-title":"Shock"},{"key":"B8","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1016\/S0303-7207(02)00106-5","article-title":"Estrogen regulation of immune responses after injury","volume":"193","author":"Kovacs","year":"2002","journal-title":"Mol Cell Endocrinol"},{"key":"B9","doi-asserted-by":"publisher","first-page":"127","DOI":"10.2174\/187153006777442422","article-title":"Gender and susceptibility to sepsis following trauma","volume":"6","author":"Choudhry","year":"2006","journal-title":"Endocr Metab Immune Disord Drug Targets"},{"key":"B10","doi-asserted-by":"publisher","first-page":"935","DOI":"10.1001\/archsurg.134.9.935","article-title":"Male gender is a risk factor for major infections after surgery","volume":"134","author":"Offner","year":"1999","journal-title":"Arch Surg"},{"key":"B11","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1007\/s001340050041","article-title":"Incidence and mortality of severe sepsis in surgical intensive care patients: the influence of patient gender on disease process and outcome","volume":"26","author":"Wichmann","year":"2000","journal-title":"Intensive Care Med"},{"key":"B12","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1097\/00024382-200014030-00011","article-title":"Gender differences in sepsis: genetically determined?","volume":"14","author":"Schroder","year":"2000","journal-title":"Shock"},{"key":"B13","doi-asserted-by":"publisher","first-page":"572","DOI":"10.1097\/TA.0b013e3181650fdf","article-title":"Male gender is associated with excessive IL-6 expression following severe injury","volume":"64","author":"Sperry","year":"2008","journal-title":"J Trauma"},{"key":"B14","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1097\/SLA.0b013e318148566","article-title":"Hormonally active women tolerate shock-trauma better than do men: a prospective study of over 4000 trauma patients","volume":"246","author":"Deitch","year":"2007","journal-title":"Ann Surg"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1110","DOI":"10.1097\/CCM.0000000000000139","article-title":"Sex- and diagnosis-dependent differences in mortality and admission cytokine levels among patients admitted for intensive care","volume":"42","author":"Guidry","year":"2014","journal-title":"Crit Care Med"},{"key":"B16","doi-asserted-by":"publisher","first-page":"1294","DOI":"10.1097\/CCM.0000000000000268","article-title":"In gender-based outcomes, sex hormones may be important but it is in the genes","volume":"42","author":"Spolarics","year":"2014","journal-title":"Crit Care Med"},{"key":"B17","doi-asserted-by":"publisher","first-page":"892","DOI":"10.1007\/s00540-012-1426-2","article-title":"The effects of estrogen on various organs: therapeutic approach for sepsis, trauma, and reperfusion injury. Part 2: liver, intestine, spleen, and kidney","volume":"26","author":"Kawasaki","year":"2012","journal-title":"J Anesth"},{"key":"B18","doi-asserted-by":"publisher","first-page":"430","DOI":"10.1097\/01.TA.0000022347.85881.A8","article-title":"Gender-related outcomes in trauma","volume":"53","author":"Mostafa","year":"2002","journal-title":"J Trauma"},{"key":"B19","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1097\/TA.0b013e3181efc67b","article-title":"Evidence of hormonal basis for improved survival among females with trauma-associated shock: an analysis of the National Trauma Data Bank","volume":"69","author":"Haider","year":"2010","journal-title":"J Trauma"},{"key":"B20","doi-asserted-by":"publisher","first-page":"1428","DOI":"10.1001\/jama.295.12.1428","article-title":"The role of X inactivation and cellular mosaicism in women\u2019s health and sex-specific diseases","volume":"295","author":"Migeon","year":"2006","journal-title":"JAMA"},{"key":"B21","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/S1550-8579(07)80024-6","article-title":"Why females are mosaics, X-chromosome inactivation, and sex differences in disease","volume":"4","author":"Migeon","year":"2007","journal-title":"Gend Med"},{"key":"B22","doi-asserted-by":"publisher","first-page":"973","DOI":"10.1016\/j.jamcollsurg.2012.02.020","article-title":"Racial disparities and sex-based outcomes differences after severe injury","volume":"214","author":"Sperry","year":"2012","journal-title":"J Am Coll Surg"},{"key":"B23","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1111\/nicc.12280","article-title":"Systematic review of gender-dependent outcomes in sepsis","volume":"22","author":"Papathanassoglou","year":"2017","journal-title":"Nurs Crit Care"},{"key":"B24","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1093\/trstmh\/tru167","article-title":"Sex-based differences in immune function and responses to vaccination","volume":"109","author":"Klein","year":"2015","journal-title":"Trans R Soc Trop Med Hyg"},{"key":"B25","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":"B26","doi-asserted-by":"publisher","first-page":"518","DOI":"10.1210\/jc.2008-0940","article-title":"Estradiol and inflammatory markers in older men","volume":"94","author":"Maggio","year":"2009","journal-title":"J Clin Endocrinol Metab"},{"key":"B27","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1196\/annals.1346.030","article-title":"Estrogen regulation of immune cell bone interactions","volume":"1068","author":"Weitzmann","year":"2006","journal-title":"Ann N Y Acad Sci"},{"key":"B28","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1210\/er.2003-0005","article-title":"Androgens and cardiovascular disease","volume":"24","author":"Liu","year":"2003","journal-title":"Endocr Rev"},{"key":"B29","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1055\/s-2004-861553","article-title":"Adrenal androgens and the immune system","volume":"22","author":"Chen","year":"2004","journal-title":"Semin Reprod Med"},{"key":"B30","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1016\/0002-9343(92)90234-3","article-title":"Risk factors for septic shock in the early management of bacteremia","volume":"93","author":"Aube","year":"1992","journal-title":"Am J Med"},{"key":"B31","doi-asserted-by":"publisher","first-page":"1076","DOI":"10.1016\/S0140-6736(88)90093-1","article-title":"Thermal burns, gender, and survival","volume":"2","author":"Barrow","year":"1988","journal-title":"Lancet"},{"key":"B32","doi-asserted-by":"publisher","first-page":"S109","DOI":"10.1097\/00003246-200107001-00035","article-title":"Epidemiology of sepsis: an update","volume":"29","author":"Angus","year":"2001","journal-title":"Crit Care Med"},{"key":"B33","first-page":"295","article-title":"Incidence of mortality in boys and girls after severe thermal burns","volume":"170","author":"Barrow","year":"1990","journal-title":"Surg Gynecol Obstet"},{"key":"B34","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1006\/jtbi.1999.1044","article-title":"Natural selection and sex differences in morbidity and mortality in early life","volume":"202","author":"Wells","year":"2000","journal-title":"J Theor Biol"},{"key":"B35","doi-asserted-by":"publisher","first-page":"594","DOI":"10.1038\/nri2815","article-title":"The X chromosome in immune functions: when a chromosome makes the difference","volume":"10","author":"Libert","year":"2010","journal-title":"Nat Rev Immunol"},{"key":"B36","doi-asserted-by":"publisher","first-page":"1786","DOI":"10.1378\/chest.07-0420","article-title":"Influence of gender on the outcome of severe sepsis: a reappraisal","volume":"132","author":"Adrie","year":"2007","journal-title":"Chest"},{"key":"B37","doi-asserted-by":"publisher","first-page":"S111","DOI":"10.1093\/geronb\/51B.3.S111","article-title":"Differentials in active life expectancy in the older population of the United States","volume":"51","author":"Crimmins","year":"1996","journal-title":"J Gerontol B Psychol Sci Soc Sci"},{"key":"B38","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1016\/j.jss.2012.06.010","article-title":"17beta-Estradiol reappropriates mass lost to the hypermetabolic state in thermally injured rats","volume":"181","author":"Abdelfattah","year":"2013","journal-title":"J Surg Res"},{"key":"B39","doi-asserted-by":"publisher","first-page":"12","DOI":"10.4161\/viru.26982","article-title":"Gender differences in sepsis: cardiovascular and immunological aspects","volume":"5","author":"Angele","year":"2014","journal-title":"Virulence"},{"key":"B40","doi-asserted-by":"publisher","first-page":"1838","DOI":"10.1097\/CCM.0b013e3181760c14","article-title":"Characterization of the gender dimorphism after injury and hemorrhagic shock: are hormonal differences responsible?","volume":"36","author":"Sperry","year":"2008","journal-title":"Crit Care Med"},{"key":"B41","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1159\/000126741","article-title":"Fast glucocorticoid feedback inhibition of ACTH secretion in the ovariectomized rat: effect of chronic estrogen and progesterone","volume":"60","author":"Redei","year":"1994","journal-title":"Neuroendocrinology"},{"key":"B42","doi-asserted-by":"publisher","first-page":"1819","DOI":"10.1016\/j.metabol.2013.08.014","article-title":"Gender determines ACTH recovery from hypercortisolemia in healthy older humans","volume":"62","author":"Sharma","year":"2013","journal-title":"Metabolism"},{"key":"B43","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1016\/j.mehy.2003.12.005","article-title":"Cortisol abnormality as a cause of elevated estrogen and immune destabilization: insights for human medicine from a veterinary perspective","volume":"62","author":"Plechner","year":"2004","journal-title":"Med Hypotheses"},{"key":"B44","doi-asserted-by":"publisher","first-page":"R627","DOI":"10.1152\/ajpregu.00551.2013","article-title":"Estradiol, but not testosterone, heightens cortisol-mediated negative feedback on pulsatile ACTH secretion and ACTH approximate entropy in unstressed older men and women","volume":"306","author":"Sharma","year":"2014","journal-title":"Am J Physiol Regul Integr Comp Physiol"},{"key":"B45","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1095\/biolreprod60.1.164","article-title":"Effect of stress-like concentrations of cortisol on estradiol-dependent expression of gonadotropin-releasing hormone receptor in orchidectomized sheep","volume":"60","author":"Adams","year":"1999","journal-title":"Biol Reprod"},{"key":"B46","first-page":"2248","article-title":"Functional polymorphism in exon 5 and variant haplotype of the interleukin-1 receptor-associated kinase 1 gene are associated with susceptibility to and severity of sepsis in the Chinese population","volume":"124","author":"Fang","year":"2011","journal-title":"Chin Med J (Engl)"},{"key":"B47","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1038\/icb.2009.39","article-title":"X chromosome reactivation perturbs intracellular self\/not-self discrimination","volume":"87","author":"Forsdyke","year":"2009","journal-title":"Immunol Cell Biol"},{"key":"B48","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1097\/SHK.0b013e31802e40bd","article-title":"The X-files of inflammation: cellular mosaicism of X-linked polymorphic genes and the female advantage in the host response to injury and infection","volume":"27","author":"Spolarics","year":"2007","journal-title":"Shock"},{"key":"B49","doi-asserted-by":"publisher","first-page":"2003","DOI":"10.1097\/CCM.0b013e3181eb9ed6","article-title":"Female X-chromosome mosaicism for gp91phox expression diversifies leukocyte responses during endotoxemia","volume":"38","author":"Chandra","year":"2010","journal-title":"Crit Care Med"},{"key":"B50","doi-asserted-by":"publisher","first-page":"6465","DOI":"10.4049\/jimmunol.1100205","article-title":"Female X-chromosome mosaicism for NOX2 deficiency presents unique inflammatory phenotype and improves outcome in polymicrobial sepsis","volume":"186","author":"Chandra","year":"2011","journal-title":"J Immunol"},{"key":"B51","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1189\/jlb.0713397","article-title":"Cellular mosaicism for X-linked polymorphisms and IRAK1 expression presents a distinct phenotype and improves survival following sepsis","volume":"95","author":"Chandra","year":"2014","journal-title":"J Leukoc Biol"},{"key":"B52","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1097\/SHK.0000000000000764","article-title":"Trauma-induced acute X chromosome skewing in white blood cells represents an immuno-modulatory mechanism unique to females and a likely contributor to sex-based outcome differences","volume":"47","author":"Pena","year":"2017","journal-title":"Shock"},{"key":"B53","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1038\/nrg1247","article-title":"The X chromosome in population genetics","volume":"5","author":"Schaffner","year":"2004","journal-title":"Nat Rev Genet"},{"key":"B54","doi-asserted-by":"publisher","first-page":"1614","DOI":"10.1126\/science.1124309","article-title":"Positive natural selection in the human lineage","volume":"312","author":"Sabeti","year":"2006","journal-title":"Science"},{"key":"B55","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1038\/nature03479","article-title":"X-inactivation profile reveals extensive variability in X-linked gene expression in females","volume":"434","author":"Carrel","year":"2005","journal-title":"Nature"},{"key":"B56","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1128\/MMBR.62.2.362-378.1998","article-title":"Regulation of X-chromosome inactivation in development in mice and humans","volume":"62","author":"Goto","year":"1998","journal-title":"Microbiol Mol Biol Rev"},{"key":"B57","doi-asserted-by":"publisher","first-page":"1848","DOI":"10.1101\/gad.1422906","article-title":"Dosage compensation in mammals: fine-tuning the expression of the X chromosome","volume":"20","author":"Heard","year":"2006","journal-title":"Genes Dev"},{"key":"B58","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1016\/j.tig.2004.12.003","article-title":"X chromosome imprinting and inactivation in preimplantation mammalian embryos","volume":"21","author":"Latham","year":"2005","journal-title":"Trends Genet"},{"key":"B59","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1038\/434279a","article-title":"Genome biology: she moves in mysterious ways","volume":"434","author":"Gunter","year":"2005","journal-title":"Nature"},{"key":"B60","doi-asserted-by":"publisher","first-page":"3862","DOI":"10.1073\/pnas.95.7.3862","article-title":"An X chromosome gene regulates hematopoietic stem cell kinetics","volume":"95","author":"Abkowitz","year":"1998","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B61","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1111\/j.1399-0004.2004.00310.x","article-title":"The dynamics of X-inactivation skewing as women age","volume":"66","author":"Hatakeyama","year":"2004","journal-title":"Clin Genet"},{"key":"B62","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1093\/jnci\/91.4.304","article-title":"Skewed X-chromosome inactivation: cause or consequence?","volume":"91","author":"Brown","year":"1999","journal-title":"J Natl Cancer Inst"},{"key":"B63","doi-asserted-by":"publisher","first-page":"3472","DOI":"10.1182\/blood-2008-12-195677","article-title":"Skewing of X-inactivation ratios in blood cells of aging women is confirmed by independent methodologies","volume":"113","author":"Busque","year":"2009","journal-title":"Blood"},{"key":"B64","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1172\/JCI34470","article-title":"A skewed view of X chromosome inactivation","volume":"118","author":"Minks","year":"2008","journal-title":"J Clin Invest"},{"key":"B65","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1038\/sj.leu.2402379","article-title":"Acquired skewing of lyonization remains stable for a prolonged period in healthy blood donors","volume":"16","author":"van Dijk","year":"2002","journal-title":"Leukemia"},{"key":"B66","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1186\/gm110","article-title":"Sex chromosomes and genetic association studies","volume":"1","author":"Clayton","year":"2009","journal-title":"Genome Med"},{"key":"B67","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1038\/nature03440","article-title":"The DNA sequence of the human X chromosome","volume":"434","author":"Ross","year":"2005","journal-title":"Nature"},{"key":"B68","doi-asserted-by":"publisher","first-page":"698","DOI":"10.1097\/SLA.0000000000000918","article-title":"X chromosome-linked IRAK-1 polymorphism is a strong predictor of multiple organ failure and mortality postinjury","volume":"260","author":"Sperry","year":"2014","journal-title":"Ann Surg"},{"key":"B69","doi-asserted-by":"publisher","first-page":"2287","DOI":"10.1097\/CCM.0b013e3181f9f9c7","article-title":"IRAK1 functional genetic variant affects severity of septic shock","volume":"38","author":"Toubiana","year":"2010","journal-title":"Crit Care Med"},{"key":"B70","doi-asserted-by":"publisher","first-page":"1335","DOI":"10.1164\/rccm.200603-341OC","article-title":"Variant IRAK-1 haplotype is associated with increased nuclear factor-kappaB activation and worse outcomes in sepsis","volume":"173","author":"Arcaroli","year":"2006","journal-title":"Am J Respir Crit Care Med"},{"key":"B71","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.coi.2005.11.012","article-title":"How toll-like receptors signal: what we know and what we don\u2019t know","volume":"18","author":"O\u2019Neill","year":"2006","journal-title":"Curr Opin Immunol"},{"key":"B72","doi-asserted-by":"publisher","first-page":"40653","DOI":"10.1074\/jbc.M402666200","article-title":"The role of interleukin 1 receptor-associated kinase-4 (IRAK-4) kinase activity in IRAK-4-mediated signaling","volume":"279","author":"Lye","year":"2004","journal-title":"J Biol Chem"},{"key":"B73","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1016\/S1097-2765(03)00053-4","article-title":"Functional diversity and regulation of different interleukin-1 receptor-associated kinase (IRAK) family members","volume":"11","author":"Janssens","year":"2003","journal-title":"Mol Cell"},{"key":"B74","doi-asserted-by":"publisher","first-page":"2195","DOI":"10.1101\/gad.1228704","article-title":"Signaling to NF-kappaB","volume":"18","author":"Hayden","year":"2004","journal-title":"Genes Dev"},{"key":"B75","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1016\/j.cellsig.2007.08.009","article-title":"IRAK1: a critical signaling mediator of innate immunity","volume":"20","author":"Gottipati","year":"2008","journal-title":"Cell Signal"},{"key":"B76","doi-asserted-by":"publisher","first-page":"51697","DOI":"10.1074\/jbc.M410369200","article-title":"IRAK1 serves as a novel regulator essential for lipopolysaccharide-induced interleukin-10 gene expression","volume":"279","author":"Huang","year":"2004","journal-title":"J Biol Chem"},{"key":"B77","doi-asserted-by":"crossref","first-page":"978","DOI":"10.4049\/jimmunol.163.2.978","article-title":"Impaired cytokine signaling in mice lacking the IL-1 receptor-associated kinase","volume":"163","author":"Thomas","year":"1999","journal-title":"J Immunol"},{"key":"B78","doi-asserted-by":"publisher","first-page":"1014","DOI":"10.4049\/jimmunol.1200857","article-title":"Molecular mechanisms responsible for the selective and low-grade induction of proinflammatory mediators in murine macrophages by lipopolysaccharide","volume":"189","author":"Maitra","year":"2012","journal-title":"J Immunol"},{"key":"B79","doi-asserted-by":"publisher","first-page":"1503","DOI":"10.1007\/s10753-013-9692-1","article-title":"IRAK1-dependent signaling mediates mortality in polymicrobial sepsis","volume":"36","author":"Chandra","year":"2013","journal-title":"Inflammation"},{"key":"B80","doi-asserted-by":"publisher","first-page":"1268","DOI":"10.1016\/j.micinf.2004.08.009","article-title":"IL-1 receptor-associated kinase 1 mediates protection against Staphylococcus aureus infection","volume":"6","author":"Verdrengh","year":"2004","journal-title":"Microbes Infect"},{"key":"B81","doi-asserted-by":"publisher","first-page":"2833","DOI":"10.4049\/jimmunol.170.6.2833","article-title":"IL-1 receptor-associated kinase 1 regulates susceptibility to organ-specific autoimmunity","volume":"170","author":"Deng","year":"2003","journal-title":"J Immunol"},{"key":"B82","doi-asserted-by":"publisher","first-page":"4301","DOI":"10.4049\/jimmunol.164.8.4301","article-title":"IL-1 receptor-associated kinase modulates host responsiveness to endotoxin","volume":"164","author":"Swantek","year":"2000","journal-title":"J Immunol"},{"key":"B83","doi-asserted-by":"publisher","first-page":"H829","DOI":"10.1152\/ajpheart.00416.2001","article-title":"IRAK contributes to burn-triggered myocardial contractile dysfunction","volume":"283","author":"Thomas","year":"2002","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"B84","doi-asserted-by":"publisher","first-page":"H597","DOI":"10.1152\/ajpheart.0655.2001","article-title":"IRAK1 deletion disrupts cardiac Toll\/IL-1 signaling and protects against contractile dysfunction","volume":"285","author":"Thomas","year":"2003","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"B85","doi-asserted-by":"publisher","first-page":"4125","DOI":"10.4049\/jimmunol.179.6.4125","article-title":"Variant IL-1 receptor-associated kinase-1 mediates increased NF-kappa B activity","volume":"179","author":"Liu","year":"2007","journal-title":"J Immunol"},{"key":"B86","doi-asserted-by":"publisher","first-page":"6256","DOI":"10.1073\/pnas.0901181106","article-title":"Identification of IRAK1 as a risk gene with critical role in the pathogenesis of systemic lupus erythematosus","volume":"106","author":"Jacob","year":"2009","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B87","doi-asserted-by":"publisher","first-page":"3493","DOI":"10.1002\/art.30563","article-title":"Identification of novel genetic susceptibility loci in African American lupus patients in a candidate gene association study","volume":"63","author":"Sanchez","year":"2011","journal-title":"Arthritis Rheum"},{"key":"B88","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1136\/annrheumdis-2012-201851","article-title":"Fine mapping of Xq28: both MECP2 and IRAK1 contribute to risk for systemic lupus erythematosus in multiple ancestral groups","volume":"72","author":"Kaufman","year":"2013","journal-title":"Ann Rheum Dis"},{"key":"B89","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1359\/jbmr.2003.18.3.419","article-title":"Association of a haplotype (196Phe\/532Ser) in the interleukin-1-receptor-associated kinase (IRAK1) gene with low radial bone mineral density in two independent populations","volume":"18","author":"Ishida","year":"2003","journal-title":"J Bone Miner Res"},{"key":"B90","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1016\/j.autrev.2017.01.007","article-title":"Gender balance in patients with systemic lupus erythematosus","volume":"16","author":"Margery-Muir","year":"2017","journal-title":"Autoimmun Rev"},{"key":"B91","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/S1550-8579(04)80006-8","article-title":"Gender differences in systemic lupus erythematosus","volume":"1","author":"Yacoub Wasef","year":"2004","journal-title":"Gend Med"},{"key":"B92","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1016\/j.jaut.2016.06.020","article-title":"The critical role of epigenetics in systemic lupus erythematosus and autoimmunity","volume":"74","author":"Long","year":"2016","journal-title":"J Autoimmun"},{"key":"B93","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":"B94","first-page":"20472","article-title":"Increased activation of toll-like receptors-7 and -8 of peripheral blood mononuclear cells and upregulated serum cytokines in patients with pediatric systemic lupus erythematosus","volume":"8","author":"Guo","year":"2015","journal-title":"Int J Clin Exp Med"},{"key":"B95","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1177\/0961203315622823","article-title":"Association between toll-like receptor polymorphisms and systemic lupus erythematosus: a meta-analysis update","volume":"25","author":"Lee","year":"2016","journal-title":"Lupus"},{"key":"B96","doi-asserted-by":"publisher","first-page":"1069","DOI":"10.1002\/humu.21321","article-title":"Genetic modulation of TLR8 response following bacterial phagocytosis","volume":"31","author":"Gantier","year":"2010","journal-title":"Hum Mutat"},{"key":"B97","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1186\/1471-2350-13-66","article-title":"Toll-like receptor gene polymorphisms are associated with allergic rhinitis: a case control study","volume":"13","author":"Nilsson","year":"2012","journal-title":"BMC Med Genet"},{"key":"B98","doi-asserted-by":"publisher","first-page":"1623","DOI":"10.1093\/infdis\/jit807","article-title":"Toll-like receptor polymorphism associations with HIV-1 outcomes among sub-Saharan Africans","volume":"209","author":"Mackelprang","year":"2014","journal-title":"J Infect Dis"},{"key":"B99","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1111\/tan.12479","article-title":"Association of toll-like receptor 7 and 8 gene polymorphisms with Graves\u2019 disease in Chinese Cantonese population","volume":"85","author":"Xiao","year":"2015","journal-title":"Tissue Antigens"},{"key":"B100","first-page":"569","article-title":"Associations of toll-like receptor 7 and 8 polymorphisms with asthma and asthma-related phenotypes in a Chinese Han population","volume":"14","author":"Zhang","year":"2015","journal-title":"Iran J Allergy Asthma Immunol"},{"key":"B101","doi-asserted-by":"publisher","first-page":"2956","DOI":"10.1038\/s41598-017-03429-x","article-title":"Polymorphism in the gene encoding toll-like receptor 10 may be associated with asthma after bronchiolitis","volume":"7","author":"Tormanen","year":"2017","journal-title":"Sci Rep"},{"key":"B102","doi-asserted-by":"publisher","first-page":"7114","DOI":"10.4049\/jimmunol.177.10.7114","article-title":"Flavivirus activation of plasmacytoid dendritic cells delineates key elements of TLR7 signaling beyond endosomal recognition","volume":"177","author":"Wang","year":"2006","journal-title":"J Immunol"},{"key":"B103","doi-asserted-by":"publisher","first-page":"5598","DOI":"10.1073\/pnas.0400937101","article-title":"Recognition of single-stranded RNA viruses by toll-like receptor 7","volume":"101","author":"Lund","year":"2004","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B104","doi-asserted-by":"publisher","first-page":"7221","DOI":"10.1016\/j.vaccine.2011.07.022","article-title":"The pathogenesis of dengue","volume":"29","author":"Whitehorn","year":"2011","journal-title":"Vaccine"},{"key":"B105","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1007\/s00251-011-0574-0","article-title":"Toll-like receptor 7 and 8 polymorphisms: associations with functional effects and cellular and antibody responses to measles virus and vaccine","volume":"64","author":"Clifford","year":"2012","journal-title":"Immunogenetics"},{"key":"B106","doi-asserted-by":"publisher","first-page":"3311","DOI":"10.1128\/IAI.70.7.3311-3317.2002","article-title":"Host-pathogen interactions: subversion and utilization of the NF-kappa B pathway during infection","volume":"70","author":"Tato","year":"2002","journal-title":"Infect Immun"},{"key":"B107","doi-asserted-by":"publisher","first-page":"1524","DOI":"10.4161\/cc.3.12.1321","article-title":"NF-kappaB and JNK: an intricate affair","volume":"3","author":"Bubici","year":"2004","journal-title":"Cell Cycle"},{"key":"B108","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1038\/ncb1384","article-title":"NEMO is a sensor of Lys 63-linked polyubiquitination and functions in NF-kappaB activation","volume":"8","author":"Wu","year":"2006","journal-title":"Nat Cell Biol"},{"key":"B109","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1016\/j.molcel.2006.03.026","article-title":"Activation of IKK by TNFalpha requires site-specific ubiquitination of RIP1 and polyubiquitin binding by NEMO","volume":"22","author":"Ea","year":"2006","journal-title":"Mol Cell"},{"key":"B110","doi-asserted-by":"publisher","first-page":"R1040","DOI":"10.1016\/j.cub.2004.11.040","article-title":"Inflammatory diseases: is ubiquitinated NEMO at the hub?","volume":"14","author":"Burns","year":"2004","journal-title":"Curr Biol"},{"key":"B111","doi-asserted-by":"publisher","first-page":"1110","DOI":"10.1126\/science.1124540","article-title":"Cell biology. The stress of finding NEMO","volume":"311","author":"Bartek","year":"2006","journal-title":"Science"},{"key":"B112","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1038\/sj.onc.1209815","article-title":"NF-kappaB activation by combinations of NEMO SUMOylation and ATM activation stresses in the absence of DNA damage","volume":"26","author":"Wuerzberger-Davis","year":"2006","journal-title":"Oncogene"},{"key":"B113","doi-asserted-by":"publisher","first-page":"986","DOI":"10.1038\/ncb1458","article-title":"PIASy mediates NEMO sumoylation and NF-kappaB activation in response to genotoxic stress","volume":"8","author":"Mabb","year":"2006","journal-title":"Nat Cell Biol"},{"key":"B114","doi-asserted-by":"publisher","first-page":"466","DOI":"10.1038\/35013114","article-title":"Genomic rearrangement in NEMO impairs NF-kappaB activation and is a cause of incontinentia pigmenti. The International Incontinentia Pigmenti (IP) Consortium","volume":"405","author":"Smahi","year":"2000","journal-title":"Nature"},{"key":"B115","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1016\/j.gde.2006.04.013","article-title":"NEMO, NFkappaB signaling and incontinentia pigmenti","volume":"16","author":"Nelson","year":"2006","journal-title":"Curr Opin Genet Dev"},{"key":"B116","doi-asserted-by":"publisher","first-page":"10489","DOI":"10.1074\/jbc.M508892200","article-title":"MyD88 adapter-like (Mal) is phosphorylated by Bruton\u2019s tyrosine kinase during TLR2 and TLR4 signal transduction","volume":"281","author":"Gray","year":"2006","journal-title":"J Biol Chem"},{"key":"B117","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.imlet.2003.11.017","article-title":"Bruton\u2019s tyrosine kinase (Btk)-the critical tyrosine kinase in LPS signalling?","volume":"92","author":"Jefferies","year":"2004","journal-title":"Immunol Lett"},{"key":"B118","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1002\/(SICI)1098-1004(1999)13:4<280::AID-HUMU3>3.0.CO;2-L","article-title":"Mutations of the human BTK gene coding for bruton tyrosine kinase in X-linked agammaglobulinemia","volume":"13","author":"Vihinen","year":"1999","journal-title":"Hum Mutat"},{"key":"B119","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1111\/j.0105-2896.2005.00225.x","article-title":"Bruton\u2019s tyrosine kinase: cell biology, sequence conservation, mutation spectrum, siRNA modifications, and expression profiling","volume":"203","author":"Lindvall","year":"2005","journal-title":"Immunol Rev"},{"key":"B120","doi-asserted-by":"publisher","first-page":"690","DOI":"10.1016\/j.jaci.2005.04.043","article-title":"A genotype-phenotype correlation study in a group of 54 patients with X-linked agammaglobulinemia","volume":"116","author":"Lopez-Granados","year":"2005","journal-title":"J Allergy Clin Immunol"},{"key":"B121","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1007\/s12041-013-0213-7","article-title":"Genetic polymorphism in FOXP3 gene: imbalance in regulatory T-cell role and development of human diseases","volume":"92","author":"Oda","year":"2013","journal-title":"J Genet"},{"key":"B122","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1016\/j.gene.2013.08.066","article-title":"FoxP3 genetic variants and risk of non-small cell lung cancer in the Chinese Han population","volume":"531","author":"He","year":"2013","journal-title":"Gene"},{"key":"B123","doi-asserted-by":"publisher","first-page":"2795","DOI":"10.3892\/ol.2014.2585","article-title":"Association between FOXP3 promoter polymorphisms and cancer risk: a meta-analysis","volume":"8","author":"Jiang","year":"2014","journal-title":"Oncol Lett"},{"key":"B124","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1016\/j.intimp.2015.12.022","article-title":"Effect of FOXP3 polymorphism on the clinical outcomes after allogeneic hematopoietic stem cell transplantation in pediatric acute leukemia patients","volume":"31","author":"Piao","year":"2016","journal-title":"Int Immunopharmacol"},{"key":"B125","doi-asserted-by":"publisher","first-page":"188","DOI":"10.3760\/cma.j.issn.0578-1426.2017.03.008","article-title":"[Association of ulcerative colitis with fork head\/winged helix transcription factor-3 gene polymorphisms in Chinese patients]","volume":"56","author":"Zhang","year":"2017","journal-title":"Zhonghua Nei Ke Za Zhi"},{"key":"B126","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1080\/10245332.2016.1238645","article-title":"Association of aplastic anemia and FoxP3 gene polymorphisms in Koreans","volume":"22","author":"In","year":"2017","journal-title":"Hematology"},{"key":"B127","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1186\/1475-2875-12-9","article-title":"Genetic evidence of regulatory gene variants of the STAT6, IL10R and FOXP3 locus as a susceptibility factor in uncomplicated malaria and parasitaemia in Congolese children","volume":"12","author":"Koukouikila-Koussounda","year":"2013","journal-title":"Malar J"},{"key":"B128","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1002\/jlb.63.5.534","article-title":"Endotoxemia, pentose cycle, and the oxidant\/antioxidant balance in the hepatic sinusoid","volume":"63","author":"Spolarics","year":"1998","journal-title":"J Leukoc Biol"},{"key":"B129","first-page":"3367","article-title":"Glucose 6 phosphate dehydrogenase deficiency","volume-title":"The Metabolic and Molecular Bases of Inherited Disease","author":"Luzzatto","year":"1995"},{"key":"B130","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/S0268-960X(96)90019-3","article-title":"G6PD: population genetics and clinical manifestations","volume":"10","author":"Beutler","year":"1996","journal-title":"Blood Rev"},{"key":"B131","first-page":"239","article-title":"Neutrophils and monocytes from subjects with the Mediterranean G6PD variant: effect of Plasmodium falciparum hemozoin on G6PD activity, oxidative burst and cytokine production","volume":"9","author":"Mordmuller","year":"1998","journal-title":"Eur Cytokine Netw"},{"key":"B132","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1189\/jlb.0105010","article-title":"Augmented IL-10 production and redox-dependent signaling pathways in glucose-6-phosphate dehydrogenase-deficient mouse peritoneal macrophages","volume":"78","author":"Wilmanski","year":"2005","journal-title":"J Leukoc Biol"},{"key":"B133","doi-asserted-by":"publisher","first-page":"728","DOI":"10.1097\/00003246-200104000-00005","article-title":"Increased incidence of sepsis and altered monocyte functions in severely injured type A- glucose-6-phosphate dehydrogenase-deficient African American trauma patients","volume":"29","author":"Spolarics","year":"2001","journal-title":"Crit Care Med"},{"key":"B134","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1111\/j.1365-2362.2006.01619.x","article-title":"Skewing of X-chromosome inactivation in three generations of carriers with X-linked chronic granulomatous disease within one family","volume":"36","author":"Koker","year":"2006","journal-title":"Eur J Clin Invest"},{"key":"B135","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1007\/s00439-004-1208-5","article-title":"Characterization of six novel mutations in the CYBB gene leading to different sub-types of X-linked chronic granulomatous disease","volume":"116","author":"Stasia","year":"2005","journal-title":"Hum Genet"},{"key":"B136","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1002\/ajh.20424","article-title":"Acute lymphoblastic leukemia in a patient with chronic granulomatous disease and a novel mutation in CYBB: first report","volume":"80","author":"Wolach","year":"2005","journal-title":"Am J Hematol"},{"key":"B137","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1016\/j.gene.2005.11.036","article-title":"A splice-supporting intronic mutation in the last bp position of a cryptic exon within intron 6 of the CYBB gene induces its incorporation into the mRNA causing chronic granulomatous disease (CGD)","volume":"371","author":"Rump","year":"2006","journal-title":"Gene"},{"key":"B138","doi-asserted-by":"publisher","first-page":"528","DOI":"10.1016\/j.exphem.2006.01.005","article-title":"Characterization of 17 new cases of X-linked chronic granulomatous disease with seven novel mutations in the CYBB gene","volume":"34","author":"von Goessel","year":"2006","journal-title":"Exp Hematol"},{"key":"B139","doi-asserted-by":"publisher","first-page":"791","DOI":"10.1002\/bies.201100047","article-title":"X-chromosome-located microRNAs in immunity: might they explain male\/female differences? The X chromosome-genomic context may affect X-located miRNAs and downstream signaling, thereby contributing to the enhanced immune response of females","volume":"33","author":"Pinheiro","year":"2011","journal-title":"Bioessays"},{"key":"B140","doi-asserted-by":"publisher","first-page":"E1852","DOI":"10.3390\/ijms17111852","article-title":"X-linked miRNAs associated with gender differences in rheumatoid arthritis","volume":"17","author":"Khalifa","year":"2016","journal-title":"Int J Mol Sci"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"http:\/\/journal.frontiersin.org\/article\/10.3389\/fimmu.2017.01455\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T11:52:12Z","timestamp":1693223532000},"score":1,"resource":{"primary":{"URL":"http:\/\/journal.frontiersin.org\/article\/10.3389\/fimmu.2017.01455\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,11,13]]},"references-count":140,"alternative-id":["10.3389\/fimmu.2017.01455"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2017.01455","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,11,13]]},"article-number":"1455"}}