The X chromosome in immune functions: when a chromosome makes the difference (original) (raw)

• Aspinall, R. Longevity and the immune response. Biogerontology 1, 273–278 (2000).
  Article CAS PubMed Google Scholar
• Choudhry, M. A., Bland, K. I. & Chaudry, I. H. Gender and susceptibility to sepsis following trauma. Endocr. Metab. Immune Disord. Drug Targets 6, 127–135 (2006).
  Article CAS PubMed Google Scholar
• Gannon, C. J., Pasquale, M., Tracy, J. K., McCarter, R. J. & Napolitano, L. M. Male gender is associated with increased risk for postinjury pneumonia. Shock 21, 410–414 (2004).
  Article PubMed Google Scholar
• Butterworth, M., McClellan, B. & Aklansmith, M. Influence of sex on immunoglobulin levels. Nature 214, 1224–1225 (1967).
  Article CAS PubMed Google Scholar
• Purtilo, D. T. & Sullivan, J. L. Immunological bases for superior survival of females. Am. J. Dis. Child. 133, 1251–1253 (1979).
  CAS PubMed Google Scholar
• Burch, P. R. J. & Rowell, N. R. Genetic origin of some sex differences among human beings. Pediatrics 36, 658–659 (1965).
  Google Scholar
• Migeon, B. R. Females are mosaics: X inactivation and sex differences in disease (Oxford University Press, New York, 2007).
  Google Scholar
• Glezen, W. P. et al. Epidemiologic patterns of acute lower respiratory disease of children in a pediatric group practice. J. Pediatr. 78, 397–406 (1971).
  Article CAS PubMed Google Scholar
• Hall, C. B., Kopelman, A. E., Douglas, R. G., Geiman, J. M. & Meagher, M. P. Neonatal respiratory syncytial virus-infection. N. Engl. J. Med. 300, 393–396 (1979).
  Article CAS PubMed Google Scholar
• Kunin, C. M. Antibody distribution against non-enteropathic E. coli. Arch. Intern. Med. 110, 676–686 (1962).
  Article Google Scholar
• Thompson, D. J., Gezon, H. M., Rogers, K. D., Yee, R. B. & Hatch, T. F. Excess risk of staphylococcal infection and disease in newborn males. Am. J. Epidemiol. 84, 314–328 (1966).
  Article CAS PubMed Google Scholar
• Strachan, N. J. C. et al. Sexual dimorphism in campylobacteriosis. Epidemiol. Infect. 136, 1492–1495 (2008).
  Article CAS PubMed Google Scholar
• Green, M. S. The male predominance in the incidence of infectious diseases in children: a postulated explanation for disparities in the literature. Int. J. Epidemiol. 21, 381–386 (1992).
  Article CAS PubMed Google Scholar
• Restif, O. & William, A. The evolution of sex-specific immune defenses. Proc. R. Soc. Lond. B Biol. Sci. Mar 24 2010 (doi:10.1098/rspb.2010.0188).
  Article PubMed PubMed Central Google Scholar
• Migeon, B. R. The role of X inactivation and cellular mosaicism in women's health and sex-specific diseases. JAMA 295, 1428–1433 (2006).
  Article CAS PubMed Google Scholar
• Morris, J. A. & Harrison, L. M. Hypothesis: increased male mortality caused by infection is due to a decrease in heterozygous loci as a result of a single X chromosome. Med. Hypotheses 72, 322–324 (2009).
  Article CAS PubMed Google Scholar
• Spolarics, Z. The X-files of inflammation: cellular mosaicism of X-linked polymorphic genes and the female advantage in the host response to injury and infection. Shock 27, 597–604 (2007).
  Article CAS PubMed Google Scholar
• Arnold, A. P. Sex chromosomes and brain gender. Nature Rev. Neurosci. 5, 701–708 (2004).
  Article CAS Google Scholar
• Lleo, A., Battezzati, P. M., Selmi, C., Gershwin, M. E. & Podda, M. Is autoimmunity a matter of sex? Autoimmun. Rev. 7, 626–630 (2008).
  Article CAS PubMed Google Scholar
• Ozcelik, T. X chromosome inactivation and female predisposition to autoimmunity. Clin. Rev. Allergy Immunol. 34, 348–351 (2008).
  Article PubMed Google Scholar
• Selmi, C. The X in sex: how autoimmune diseases revolve around sex chromosomes. Best Pract. Res. Clin. Rheumatol. 22, 913–922 (2008).
  Article CAS PubMed Google Scholar
• Deitch, E. A. et al. Neutrophil activation is modulated by sex hormones after trauma-hemorrhagic shock and burn injuries. Am. J. Physiol. Heart Circ. Physiol. 291, 1456–1465 (2006).
  Article CAS Google Scholar
• Nalbandian, G. & Kovats, S. Understanding sex biases in immunity — effects of estrogen on the differentiation and function of antigen-presenting cells. Immunol. Res. 31, 91–106 (2005).
  Article CAS PubMed Google Scholar
• Szalay, L. et al. Androstenediol administration after trauma-hemorrhage attenuates inflammatory response, reduces organ damage, and improves survival following sepsis. Am. J. Physiol. Gastrointest. Liver Physiol. 291, 260–266 (2006).
  Article CAS Google Scholar
• Burgoyne, P. S. et al. The genetic basis of XX–XY differences present before gonadal sex differentiation in the mouse. Philos. Trans. R. Soc. Lond. B Biol. Sci. 350, 253–260 (1995).
  Article CAS PubMed Google Scholar
• Palaszynski, K. M. et al. A Yin-Yang effect between sex chromosome complement and sex hormones on the immune response. Endocrinology 146, 3280–3285 (2005).
  Article CAS PubMed Google Scholar
• Washburn, T. C., Medearis, D. N. & Childs, B. Sex differences in susceptibility to infections. Pediatrics 35, 57–64 (1965).
  CAS PubMed Google Scholar
• McMillen, M. M. Differential mortality by sex in fetal and neonatal deaths. Science 204, 89–91 (1979).
  Article CAS PubMed Google Scholar
• Forest, M. G., Cathiard, A. M. & Bertrand, J. A. Evidence of testicular activity in early infancy. J. Clin. Endocrinol. Metab. 37, 148–151 (1973).
  Article CAS PubMed Google Scholar
• Mage, D. T. & Donner, M. A genetic basis for the sudden infant death syndrome sex ratio. Med. Hypotheses 48, 137–142 (1997).
  Article CAS PubMed Google Scholar
• Morris, J. A. & Harrison, L. M. Sudden unexpected death in infancy: evidence of infection. Lancet 371, 1815–1816 (2008).
  Article PubMed Google Scholar
• Weber, M. A. et al. Infection and sudden unexpected death in infancy: a systematic retrospective case review. Lancet 371, 1848–1853 (2008).
  Article CAS PubMed Google Scholar
• Notarangelo, L. et al. Primary immunodeficiency diseases: an update from the International Union of Immunological Societies Primary Immunodeficiency Diseases Classification Committee meeting in Budapest, 2005. J. Allergy Clin. Immunol. 117, 883–896 (2006).
  Article PubMed Google Scholar
• Pessach, I. M. & Notarangelo, L. D. X-linked primary immunodeficiencies as a bridge to better understanding X-chromosome related autoimmunity. J. Autoimmun. 33, 17–24 (2009).
  Article CAS PubMed Google Scholar
• Teahan, C., Rowe, P., Parker, P., Totty, N. & Segal, A. W. The X-linked chronic granulomatous-disease gene codes for the β-chain of cytochrome-_b_-245. Nature 327, 720–721 (1987).
  Article CAS PubMed Google Scholar
• Bennett, C. et al. The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3. Nature Genet. 27, 20–21 (2001).
  Article CAS PubMed Google Scholar
• Noguchi, M. et al. Interleukin-2 receptor γ chain mutation results in X-linked severe combined immunodeficiency in humans. Cell 73, 147–157 (1993).
  Article CAS PubMed Google Scholar
• Leonard, W. J. Cytokines and immunodeficiency diseases. Nature Rev. Immunol. 1, 200–208 (2001).
  Article CAS Google Scholar
• Mordmuller, B., Turrini, F., Long, H., Kremsner, P. G. & Arese, P. Neutrophils and monocytes from subjects with the Mediterranean G6PD variant: effect of Plasmodium falciparum hemozoin on G6PD activity, oxidative burst and cytokine production. Eur. Cytokine Netw. 9, 239–245 (1998).
  CAS PubMed Google Scholar
• Wilmanski, J., Siddiqi, M., Deitch, E. A. & Spolarics, Z. Augmented IL-10 production and redox-dependent signaling pathways in glucose-6-phosphate dehydrogenase-deficient mouse peritoneal macrophages. J. Leukoc. Biol. 78, 85–94 (2005).
  Article CAS PubMed Google Scholar
• Smahi, A. et al. Genomic rearrangement in NEMO impairs NF-κB activation and is a cause of incontinentia pigmenti. The International Incontinentia Pigmenti (IP) Consortium. Nature 405, 466–472 (2000).
  Article CAS PubMed Google Scholar
• Uzel, G. The range of defects associated with nuclear factor κB essential modulator. Curr. Opin. Allergy Clin. Immunol. 5, 513–518 (2005).
  Article CAS PubMed Google Scholar
• Orange, J. S. et al. The presentation and natural history of immunodeficiency caused by nuclear factor κB essential modulator mutation. J. Allergy Clin. Immunol. 113, 725–733 (2004).
  Article CAS PubMed Google Scholar
• Orange, J. S. et al. Human nuclear factor κB essential modulator mutation can result in immunodeficiency without ectodermal dysplasia. J. Allergy Clin. Immunol. 114, 650–656 (2004).
  Article CAS PubMed Google Scholar
• Orange, J. S., Levy, O. & Geha, R. S. Human disease resulting from gene mutations that interfere with appropriate nuclear factor-κB activation. Immunol. Rev. 203, 21–37 (2005).
  Article CAS PubMed Google Scholar
• Vicoso, B. & Charlesworth, B. Evolution on the X chromosome: unusual patterns and processes. Nature Rev. Gen. 7, 645–653 (2006).
  Article CAS Google Scholar
• Ohno, S. Sex Chromosomes and Sex-Linked Genes (Springer, Berlin, 1967).
  Book Google Scholar
• Nguyen, D. K. & Disteche, C. M. Dosage compensation of the active X chromosome in mammals. Nature Genet. 38, 47–53 (2006). By comparing the global X chromosome transcriptome with that of autosomes, the authors show that mammalian X chromosome gene expression is upregulated in several somatic tissues to match the levels shown by autosomal genes.
  Article CAS PubMed Google Scholar
• Vallender, E. J. & Lahn, B. T. How mammalian sex chromosomes acquired their peculiar gene content. Bioessays 26, 159–169 (2004).
  Article CAS PubMed Google Scholar
• Wang, P. J., McCarrey, J. R., Yang, F. & Page, D. C. An abundance of X-linked genes expressed in spermatogonia. Nature Genet. 27, 422–426 (2001).
  PubMed Google Scholar
• Ross, M. T. et al. The DNA sequence of the human X chromosome. Nature 434, 325–337 (2005). This article provides the complete description of structural features of the human X chromosome, as well as a detailed analysis of its evolution and the processes that led to progressive loss of recombination between sex chromosomes.
  Article CAS PubMed PubMed Central Google Scholar
• Carrel, L. & Willard, H. F. X-inactivation profile reveals extensive variability in X-linked gene expression in females. Nature 434, 400–404 (2005). This article provides a complete profile of human X chromosome inactivation, showing for the first time that X-linked genes can escape inactivation, and that this is a heterogeneous process.
  Article CAS PubMed Google Scholar
• Johnston, C. M. et al. Large-scale population study of human cell lines indicates that dosage compensation is virtually complete. Plos Genet. 4, e9 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Wilson, M. A. & Makova, K. D. Evolution and survival on eutherian sex chromosomes. PLoS Genet. 5, e1000568 (2009). In this paper, the authors show for the first time that X and Y homologous genes have evolved at different evolutionary rates after suppression of recombination. They also show that some XY homologous genes have acquired specific mRNA or protein expression patterns and functions.
  Article CAS PubMed PubMed Central Google Scholar
• Ditton, H. J., Zimmer, J., Rajpert- De Meyts, E. & Vogt, P. H. The AZFa gene DBY (DDX3Y) is widely transcribed but the protein is limited to the male germ cells by translation control. Hum. Mol. Genet. 13, 2333–2341 (2004).
  Article CAS PubMed Google Scholar
• Decker, T. et al. The TBK-1 substrate DDX3X, a DEAD-box RNA helicase, provides innate immunity to Listeria monocytogenes. Cytokine 43, 304 (2008).
  Article Google Scholar
• Soulat, D. et al. The DEAD-box helicase DDX3X is a critical component of the TANK-binding kinase 1-dependent innate immune response. EMBO J. 27, 2135–2146 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Anderson, C. L. & Brown, C. J. Polymorphic X-chromosome inactivation of the human TIMP1 gene. Am. J. Hum. Genet. 65, 699–708 (1999).
  Article CAS PubMed PubMed Central Google Scholar
• Brown, C. J., Carrel, L. & Willard, H. F. Expression of genes from the human active and inactive X chromosomes. Am. J. Hum. Genet. 60, 1333–1343 (1997).
  Article CAS PubMed PubMed Central Google Scholar
• Vanlaere, I. & Libert, C. Matrix metalloproteinases as drug targets in infections caused by Gram-negative bacteria and in septic shock. Clin. Microbiol. Rev. 22, 224–239 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Hoffmann, U. et al. Matrix-metalloproteinases and their inhibitors are elevated in severe sepsis: prognostic value of TIMP-1 in severe sepsis. Scand. J. Infect. Dis. 38, 867–872 (2006).
  Article CAS PubMed Google Scholar
• Burkhardt, J. et al. Association of the X-chromosomal genes TIMP1 and IL9R with rheumatoid arthritis. J. Rheumatol. 36, 2149–2157 (2009).
  Article CAS PubMed Google Scholar
• Migeon, B. R. Why females are mosaics, X-chromosome inactivation, and sex differences in disease. Gend. Med. 4, 97–105 (2007). This review provides a comprehensive explanation of mosaicism in females and why males are more vulnerable to diseases than females.
  Article PubMed Google Scholar
• Migeon, B. R. Non-random X chromosome inactivation in mammalian cells. Cytogenet. Cell Genet. 80, 142–148 (1998).
  Article CAS PubMed Google Scholar
• Orstavik, K. H. X chromosome inactivation in clinical practice. Hum. Genet. 126, 363–373 (2009).
  Article PubMed Google Scholar
• Migeon, B. R. et al. Selection against lethal alleles in females heterozygous for incontinentia pigmenti. Am. J. Hum. Genet. 44, 100–106 (1989).
  CAS PubMed PubMed Central Google Scholar
• Fearon, E. R., Kohn, D. B., Winkelstein, J. A., Vogelstein, B. & Blaese, R. M. Carrier detection in the Wiskott Aldrich syndrome. Blood 72, 1735–1739 (1988).
  CAS PubMed Google Scholar
• Van den Bogaard, R. et al. Molecular characterisation of 10 Dutch properdin type I deficient families: mutation analysis and X-inactivation studies. Eur. J. Hum. Genet. 8, 513–518 (2000).
  Article CAS PubMed Google Scholar
• Gleicher, N. & Barad, D. H. Gender as risk factor for autoimmune diseases. J. Autoimmun. 28, 1–6 (2007).
  Article CAS PubMed Google Scholar
• Jacobson, D. L., Gange, S. J., Rose, N. R. & Graham, N. M. H. Epidemiology and estimated population burden of selected autoimmune diseases in the United States. Clin. Immunol. Immunopathol. 84, 223–243 (1997).
  Article CAS PubMed Google Scholar
• Kast, R. E. Hypothesis – predominance of autoimmune and rheumatic diseases in females. J. Rheumatol. 4, 288–292 (1977).
  CAS PubMed Google Scholar
• Stewart, J. J. The female X-inactivation mosaic in systemic lupus erythematosus. Immunol. Today 19, 352–357 (1998). The original description of the loss of mosaicism hypothesis. In this article, a theoretical background for this hypothesis and the main findings which corroborate it are provided.
  Article CAS PubMed Google Scholar
• Takeno, M. et al. Autoreactive T cell clones from patients with systemic lupus erythematosus support polyclonal autoantibody production. J. Immunol. 158, 3529–3538 (1997).
  CAS PubMed Google Scholar
• Scofield, R. H. et al. Klinefelter's syndrome (47,XXY) in male systemic lupus erythematosus patients: support for the notion of a gene-dose effect from the X chromosome. Arthritis Rheum. 58, 2511–2517 (2008).
  Article PubMed PubMed Central Google Scholar
• Litsuka, Y. et al. Evidence of skewed X-chromosome inactivation in 47,XXY and 48,XXYY Klinefelter patients. Am. J. Med. Genet. 98, 25–31 (2001).
  Article Google Scholar
• Brix, T. H. et al. High frequency of skewed X-chromosome inactivation in females with autoimmune thyroid disease: A possible explanation for the female predisposition to thyroid autoimmunity. J. Clin. Endocrinol. Metab. 90, 5949–5953 (2005).
  Article CAS PubMed Google Scholar
• Ozbalkan, Z. et al. Skewed X chromosome inactivation in blood cells of women with scleroderma. Arthritis Rheum. 52, 1564–1570 (2005).
  Article CAS PubMed Google Scholar
• Ozcelik, T. et al. Evidence from autoimmune thyroiditis of skewed X-chromosome inactivation in female predisposition to autoimmunity. Eur. J. Hum. Genet. 14, 791–797 (2006).
  Article CAS PubMed Google Scholar
• Uz, E. et al. Skewed X-chromosome inactivation in scleroderma. Clin. Rev. Allergy Immunol. 34, 352–355 (2008).
  Article PubMed PubMed Central Google Scholar
• Invernizzi, P. The X chromosome in female-predominant autoimmune diseases. Ann. N Y Acad. Sci. 1110, 57–64 (2007).
  Article CAS PubMed Google Scholar
• Chitnis, S. et al. The role of X-chromosome inactivation in female predisposition to autoimmunity. Arthritis Res. 2, 399–406 (2000). This study describes a large survey of patterns of X chromosome inactivation skewing in patients with different autoimmune diseases and in age-matched female controls. The authors provide a model showing the consequences of skewed inactivation on tolerance induction in the thymus.
  Article CAS PubMed PubMed Central Google Scholar
• Lu, Q. et al. Demethylation of CD40LG on the inactive X in T cells from women with lupus. J. Immunol. 179, 6352–6358 (2007). This study shows for the first time that CD40L overexpression on CD4+ T cells, owing to inactive X chromosome reactivation, contributes to the pathogenesis of SLE.
  Article CAS PubMed Google Scholar
• Forsdyke, D. R. X chromosome reactivation perturbs intracellular self/not-self discrimination. Immunol. Cell Biol. 87, 525–528 (2009).
  Article CAS PubMed Google Scholar
• Zhou, Y. et al. T cell CD40LG gene expression and the production of IgG by autologous B cells in systemic lupus erythematosus. Clin. Immunol. 132, 362–370 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Subramanian, S. et al. A Tlr7 translocation accelerates systemic autoimmunity in murine lupus. Proc. Natl Acad. Sci. USA 103, 9970–9975 (2006).
  Article CAS PubMed PubMed Central Google Scholar
• Smith-Bouvier, D. L. et al. A role for sex chromosome complement in the female bias in autoimmune disease. J. Exp. Med. 205, 1099–1108 (2008). This study provides a simple and elegant way to show how wild-type female mice are more susceptible to models of autoimmune diseases than XY Sry− mice with a common gonadal background.
  Article CAS PubMed PubMed Central Google Scholar
• Invernizzi, P. et al. X chromosome monosomy: a common mechanism for autoimmune diseases. J. Immunol. 175, 575–578 (2005).
  Article CAS PubMed Google Scholar
• Ranke, M. B. & Saenger, P. Turner's syndrome. Lancet 358, 309–314 (2001).
  Article CAS PubMed Google Scholar
• Elsheikh, M., Wass, J. A. H. & Conway, G. S. Autoimmune thyroid syndrome in women with Turner's syndrome — the association with karyotype. Clin. Endocrinol. 55, 223–226 (2001).
  Article CAS Google Scholar
• Sybert, V. P. & McCauley, E. Turner's syndrome. N. Engl. J. Med. 351, 1227–1238 (2004).
  Article CAS PubMed Google Scholar
• Bondy, C. A. & Cheng, C. Monosomy for the X chromosome. Chromosome Res. 17, 649–658 (2009). This review describes the major effects of X chromosome monosomy on Turner's syndrome. A list of X-linked genes located in the pseudoautosomal regions is given, together with the hypothesis that haploinsufficiency for these genes may be responsible for the symptoms.
  Article CAS PubMed Google Scholar
• Invernizzi, P. et al. Frequency of monosomy X in women with primary biliary cirrhosis. Lancet 363, 533–535 (2004).
  Article PubMed Google Scholar
• Baltimore, D. Our genome unveiled. Nature 409, 814–816 (2001).
  Article CAS PubMed Google Scholar
• Disteche, C. M. Escapees on the X chromosome. Proc. Natl Acad. Sci. USA 96, 14180–14182 (1999).
  Article CAS PubMed PubMed Central Google Scholar
• Disteche, C. M., Filippova, G. N. & Tsuchiya, K. D. Escape from X inactivation. Cytogenet. Genome Res. 99, 36–43 (2002). A complete and comprehensive review on the process of X inactivation, which provides a comparison between human and mouse genes that escape silencing. Considerations about the molecular characteristics of the genes that escape inactivation are also given together with possible explanations for the phenomenon.
  Article CAS PubMed Google Scholar
• Lewis, B. P., Burge, C. B. & Bartel, D. P. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 120, 15–20 (2005).
  Article CAS PubMed Google Scholar
• Guo, X. J., Su, B., Zhou, Z. M. & Sha, J. H. Rapid evolution of mammalian X-linked testis microRNAs. BMC Genomics 10, 97 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• le Sage, C. et al. Regulation of the p27(Kip1) tumor suppressor by miR-221 and miR-222 promotes cancer cell proliferation. EMBO J. 26, 3699–3708 (2007).
  Article CAS PubMed PubMed Central Google Scholar
• Johnnidis, J. B. et al. Regulation of progenitor cell proliferation and granulocyte function by microRNA-223. Nature 451, 1125–1129 (2008).
  Article CAS PubMed Google Scholar
• Fontana, L. et al. MicroRNAs 17-5p-20a-106a control monocytopoiesis through AML1 targeting and M-CSF receptor upregulation. Nature Cell Biol. 9, 775–787 (2007).
  Article CAS PubMed Google Scholar
• Rosa, A. et al. The interplay between the master transcription factor PU.1 and miR-424 regulates human monocyte/macrophage differentiation. Proc. Natl Acad. Sci. USA 104, 19849–19854 (2007).
  Article CAS PubMed PubMed Central Google Scholar
• Cooper, G. S. & Stroehla, B. C. The epidemiology of autoimmune diseases. Autoimmun. Rev. 2, 119–125 (2003).
  Article PubMed Google Scholar