Sex chromosome contributions to sex differences in multiple sclerosis susceptibility and progression

被引：53

作者：

Voskuhl, Rhonda R. ^{[1
]}

Sawalha, Amr H. ^{[2
,3
]}

Itoh, Yuichiro ^{[1
]}

机构：

[1] Univ Calif Los Angeles, Dept Neurol, Multiple Sclerosis Program, 635 Charles E Young Dr South,Neurosci Res Bldg 1, Los Angeles, CA 90095 USA

[2] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA

[3] Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA

来源：

MULTIPLE SCLEROSIS JOURNAL | 2018年 / 24卷 / 01期

关键词：

Multiple sclerosis; genetics; immunology; animal model; neurodegeneration; sex differences; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; REGULATORY T-CELLS; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; X-CHROMOSOME; Y-CHROMOSOME; CYTOKINE RESPONSES; NATURAL-HISTORY; DNA METHYLATION; GENE-EXPRESSION; OPTIC NEURITIS;

D O I：

10.1177/1352458517737394

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Background: Why are women more susceptible to multiple sclerosis, but men have worse disability progression? Sex differences in disease may be due to sex hormones, sex chromosomes, or both. Objective: Determine whether differences in sex chromosomes can contribute to sex differences in multiple sclerosis using experimental autoimmune encephalomyelitis. Methods: Sex chromosome transgenic mice, which permit the study of sex chromosomes not confounded by differences in sex hormones, were used to examine an effect of sex chromosomes on autoimmunity and neurodegeneration, focusing on X chromosome genes. Results: T-lymphocyte DNA methylation studies of the X chromosome gene Foxp3 suggested that maternal versus paternal imprinting of X chromosome genes may underlie sex differences in autoimmunity. Bone marrow chimeras with the same immune system but different sex chromosomes in the central nervous system suggested that differential expression of the X chromosome gene Toll-like receptor 7 in neurons may contribute to sex differences in neurodegeneration. Conclusion: Mapping the transcriptome and methylome in T lymphocytes and neurons in females versus males could reveal mechanisms underlying sex differences in autoimmunity and neurodegeneration.

引用

页码：22 / 31

页数：10

共 74 条

[1] MR microscopy of transgenic mice that spontaneously acquire experimental allergic encephalomyelitis [J].

Ahrens, ET ;

Laidlaw, DH ;

Readhead, C ;

Brosnan, CF ;

Fraser, SE ;

Jacobs, RE .

MAGNETIC RESONANCE IN MEDICINE, 1998, 40 (01) :119-132

[2] Are XX and XY brain cells intrinsically different? [J].

Arnold, AP ;

Burgoyne, PS .

TRENDS IN ENDOCRINOLOGY AND METABOLISM, 2004, 15 (01) :6-11

[3] What does the "four core genotypes" mouse model tell us about sex differences in the brain and other tissues? [J].

Arnold, Arthur P. ;

Chen, Xuqi .

FRONTIERS IN NEUROENDOCRINOLOGY, 2009, 30 (01) :1-9

[4] Genome-wide association analysis of susceptibility and clinical phenotype in multiple sclerosis [J].

Baranzini, Sergio E. ;

Wang, Joanne ;

Gibson, Rachel A. ;

Galwey, Nicholas ;

Naegelin, Yvonne ;

Barkhof, Frederik ;

Radue, Ernst-Wilhelm ;

Lindberg, Raija L. P. ;

Uitdehaag, Bernard M. G. ;

Johnson, Michael R. ;

Angelakopoulou, Aspasia ;

Hall, Leslie ;

Richardson, Jill C. ;

Prinjha, Rab K. ;

Gass, Achim ;

Geurts, Jeroen J. G. ;

Kragt, Jolijn ;

Sombekke, Madeleine ;

Vrenken, Hugo ;

Qualley, Pamela ;

Lincoln, Robin R. ;

Gomez, Refujia ;

Caillier, Stacy J. ;

George, Michaela F. ;

Mousavi, Hourieh ;

Guerrero, Rosa ;

Okuda, Darin T. ;

Cree, Bruce A. C. ;

Green, Ari J. ;

Waubant, Emmanuelle ;

Goodin, Douglas S. ;

Pelletier, Daniel ;

Matthews, Paul M. ;

Hauser, Stephen L. ;

Kappos, Ludwig ;

Polman, Chris H. ;

Oksenberg, Jorge R. .

HUMAN MOLECULAR GENETICS, 2009, 18 (04) :767-778

[5] Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis [J].

Beecham, Ashley H. ;

Patsopoulos, Nikolaos A. ;

Xifara, Dionysia K. ;

Davis, Mary F. ;

Kemppinen, Anu ;

Cotsapas, Chris ;

Shah, Tejas S. ;

Spencer, Chris ;

Booth, David ;

Goris, An ;

Oturai, Annette ;

Saarela, Janna ;

Fontaine, Bertrand ;

Hemmer, Bernhard ;

Martin, Claes ;

Zipp, Frauke ;

D'Alfonso, Sandra ;

Martinelli-Boneschi, Filippo ;

Taylor, Bruce ;

Harbo, Hanne F. ;

Kockum, Ingrid ;

Hillert, Jan ;

Olsson, Tomas ;

Ban, Maria ;

Oksenberg, Jorge R. ;

Hintzen, Rogier ;

Barcellos, Lisa F. ;

Agliardi, Cristina ;

Alfredsson, Lars ;

Alizadeh, Mehdi ;

Anderson, Carl ;

Andrews, Robert ;

Sondergaard, Helle Bach ;

Baker, Amie ;

Band, Gavin ;

Baranzini, Sergio E. ;

Barizzone, Nadia ;

Barrett, Jeffrey ;

Bellenguez, Celine ;

Bergamaschi, Laura ;

Bernardinelli, Luisa ;

Berthele, Achim ;

Biberacher, Viola ;

Binder, Thomas M. C. ;

Blackburn, Hannah ;

Bomfim, Izaura L. ;

Brambilla, Paola ;

Broadley, Simon ;

Brochet, Bruno ;

Brundin, Lou .

NATURE GENETICS, 2013, 45 (11) :1353-+

[6] Transgenic inhibition of astroglial NF-κB protects from optic nerve damage and retinal ganglion cell loss in experimental optic neuritis [J].

Brambilla, Roberta ;

Dvoriantchikova, Galina ;

Barakat, David ;

Ivanov, Dmitry ;

Bethea, John R. ;

Shestopalov, Valery I. .

JOURNAL OF NEUROINFLAMMATION, 2012, 9

[7] The Y* rearrangement in mice: new insights into a perplexing PAR [J].

Burgoyne, PS ;

Mahadevaiah, SK ;

Perry, J ;

Palmer, SJ ;

Ashworth, A .

CYTOGENETICS AND CELL GENETICS, 1998, 80 (1-4) :37-40

[8]

Capel B, 1995, PHILOS T ROY SOC B, V350, P260

[9] Sex chromosome genes directly affect brain sexual differentiation [J].

Carruth, LL ;

Reisert, I ;

Arnold, AP .

NATURE NEUROSCIENCE, 2002, 5 (10) :933-934

[10] The Y chromosome as a regulatory element shaping Immune cell transcriptomes and susceptibility to autoimmune disease [J].

Case, Laure K. ;

Wall, Emma H. ;

Dragon, Julie A. ;

Saligrama, Naresha ;

Krementsov, Dimitry N. ;

Moussawi, Mohamad ;

Zachary, James F. ;

Huber, Sally A. ;

Blankenhorn, Elizabeth P. ;

Teuscher, Cory .

GENOME RESEARCH, 2013, 23 (09) :1474-1485

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