Demethylation of CD40LG on the inactive X in T cells from women with lupus.

Demethylation of CD40LG on the inactive X in T cells from women with lupus. Research Abstract Details 

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Demethylation of CD40LG on the inactive X in T cells from women with lupus. Abstract Text:

Qianjin Lu,Ailing Wu,Laura Tesmer,Donna Ray,Neda Yousif,Bruce Richardson,Qianjin Lu,Ailing Wu,Laura Tesmer,Donna Ray,Neda Yousif,Bruce Richardson,

Why systemic lupus erythematosus primarily affects women is unknown. Recent evidence indicates that human lupus is an epigenetic disease characterized by impaired T cell DNA methylation. Women have two X chromosomes; one is inactivated by mechanisms including DNA methylation. We hypothesized that demethylation of sequences on the inactive X may cause gene overexpression uniquely in women, predisposing them to lupus. We therefore compared expression and methylation of CD40LG, a B cell costimulatory molecule encoded on the X chromosome, in experimentally demethylated T cells from men and women and in men and women with lupus. Controls included TNFSF7, a methylation-sensitive autosomal B cell costimulatory molecule known to be demethylated and overexpressed in lupus. Bisulfite sequencing revealed that CD40LG is unmethylated in men, while women have one methylated and one unmethylated gene. 5-Azacytidine, a DNA methyltransferase inhibitor, demethylated CD40LG and doubled its expression on CD4(+) T cells from women but not men, while increasing TNFSF7 expression equally between sexes. Similar studies demonstrated that CD40LG demethylates in CD4(+) T cells from women with lupus, and that women but not men with lupus overexpress CD40LG on CD4(+) T cells, while both overexpress TNFSF7. These studies demonstrate that regulatory sequences on the inactive X chromosome demethylate in T cells from women with lupus, contributing to CD40LG overexpression uniquely in women. Demethylation of CD40LG and perhaps other genes on the inactive X may contribute to the striking female predilection of this disease.

Demethylation of CD40LG on the inactive X in T cells from women with lupus. Publishing Authors By Initials

Q Lu,A Wu,L Tesmer,D Ray,N Yousif,B Richardson,Q Lu,A Wu,L Tesmer,D Ray,N Yousif,B Richardson,

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Demethylation of CD40LG on the inactive X in T cells from women with lupus. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Journal of immunology (Baltimore, Md. : 1950)

VOLUME: 179

Page Numbers: 6352-8

Journal Abbreviation: J. Immunol.

ISSN: 0022-1767

DAY: 1

MONTH: Nov

YEAR: 2007

Demethylation of CD40LG on the inactive X in T cells from women with lupus. Information

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LANGUAGE: eng

NlmUniqueID: 2985117

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Grant and Affiliation Information for Demethylation of CD40LG on the inactive X in T cells from women with lupus.

AFFILIATION: Department of Dermatology, Second Xiangya Hospital, Central South University, Changsha, 41011 Hunan, China.

Country: United States

AGENCY: United States NIAMS

GRANT: P30AR048310

ACRONYM: AR

MEDLINETA: J Immunol

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