MBD2 regulates T H 17 differentiation and experimental autoimmune encephalomyelitis by controlling the homeostasis of T-bet/Hlx axis

Jixin Zhong, Qilin Yu, Ping Yang, Xiaoquan Rao, Long He, Jing Fang, Yaqin Tu, Zhijun Zhang, Qiaohong Lai, Shu Zhang, Michal Kuczma, Piatr Kraj, Jun Fa Xu, Feili Gong, Jianfeng Zhou, Li Wen, Decio L. Eizirik, Jie Du, Wei Wang, Cong Yi Wang

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Unlike genetic alterations, epigenetic modifications are reversible and amenable to pharmacological interventions, which make them appealing targets for clinical therapy. However, little is known about epigenetic regulation in experimental autoimmune encephalomyelitis (EAE). Here we demonstrated that methyl-CpG-binding domain protein 2 (MBD2), an epigenetic regulator, controls autoimmunity and EAE through T-bet/Hlx. Tbx21 and Hlx underwent a DNA methylation turnover upon polarizations and a unique methylation pattern was essential for T H 17 development. Loss of Mbd2 resulted in a defect for reading the information encoded by this methylation turnover, which disrupted the homeostasis of T-bet/Hlx axis and suppressed T H 17 differentiation. DNA demethylation induced similar effect on helper T cell differentiation. Therefore, Mbd2 -/- mice were completely protected from EAE. Pathogenic splenocytes isolated from wild-type mice challenged with MOG35-55 could adoptively transfer disease to Mbd2 -/- mice. In addition, Mbd2 -/- mice reconstituted with unstimulated wild-type splenocytes developed EAE as wild-type mice did. These data would provide novel insights into epigenetic regulation of EAE.

Original languageEnglish (US)
Pages (from-to)95-104
Number of pages10
JournalJournal of Autoimmunity
Volume53
Issue numberC
DOIs
StatePublished - Jan 1 2014
Externally publishedYes

Fingerprint

Autoimmune Experimental Encephalomyelitis
Homeostasis
Epigenomics
Methylation
DNA Methylation
Helper-Inducer T-Lymphocytes
Autoimmunity
Reading
Cell Differentiation
MBD2 protein
Pharmacology
DNA

Keywords

  • EAE
  • Epigenetic
  • MBD2
  • Methylation
  • T-bet
  • T 17

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

MBD2 regulates T H 17 differentiation and experimental autoimmune encephalomyelitis by controlling the homeostasis of T-bet/Hlx axis . / Zhong, Jixin; Yu, Qilin; Yang, Ping; Rao, Xiaoquan; He, Long; Fang, Jing; Tu, Yaqin; Zhang, Zhijun; Lai, Qiaohong; Zhang, Shu; Kuczma, Michal; Kraj, Piatr; Xu, Jun Fa; Gong, Feili; Zhou, Jianfeng; Wen, Li; Eizirik, Decio L.; Du, Jie; Wang, Wei; Wang, Cong Yi.

In: Journal of Autoimmunity, Vol. 53, No. C, 01.01.2014, p. 95-104.

Research output: Contribution to journalArticle

Zhong, J, Yu, Q, Yang, P, Rao, X, He, L, Fang, J, Tu, Y, Zhang, Z, Lai, Q, Zhang, S, Kuczma, M, Kraj, P, Xu, JF, Gong, F, Zhou, J, Wen, L, Eizirik, DL, Du, J, Wang, W & Wang, CY 2014, ' MBD2 regulates T H 17 differentiation and experimental autoimmune encephalomyelitis by controlling the homeostasis of T-bet/Hlx axis ', Journal of Autoimmunity, vol. 53, no. C, pp. 95-104. https://doi.org/10.1016/j.jaut.2014.05.006
Zhong, Jixin ; Yu, Qilin ; Yang, Ping ; Rao, Xiaoquan ; He, Long ; Fang, Jing ; Tu, Yaqin ; Zhang, Zhijun ; Lai, Qiaohong ; Zhang, Shu ; Kuczma, Michal ; Kraj, Piatr ; Xu, Jun Fa ; Gong, Feili ; Zhou, Jianfeng ; Wen, Li ; Eizirik, Decio L. ; Du, Jie ; Wang, Wei ; Wang, Cong Yi. / MBD2 regulates T H 17 differentiation and experimental autoimmune encephalomyelitis by controlling the homeostasis of T-bet/Hlx axis In: Journal of Autoimmunity. 2014 ; Vol. 53, No. C. pp. 95-104.
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abstract = "Unlike genetic alterations, epigenetic modifications are reversible and amenable to pharmacological interventions, which make them appealing targets for clinical therapy. However, little is known about epigenetic regulation in experimental autoimmune encephalomyelitis (EAE). Here we demonstrated that methyl-CpG-binding domain protein 2 (MBD2), an epigenetic regulator, controls autoimmunity and EAE through T-bet/Hlx. Tbx21 and Hlx underwent a DNA methylation turnover upon polarizations and a unique methylation pattern was essential for T H 17 development. Loss of Mbd2 resulted in a defect for reading the information encoded by this methylation turnover, which disrupted the homeostasis of T-bet/Hlx axis and suppressed T H 17 differentiation. DNA demethylation induced similar effect on helper T cell differentiation. Therefore, Mbd2 -/- mice were completely protected from EAE. Pathogenic splenocytes isolated from wild-type mice challenged with MOG35-55 could adoptively transfer disease to Mbd2 -/- mice. In addition, Mbd2 -/- mice reconstituted with unstimulated wild-type splenocytes developed EAE as wild-type mice did. These data would provide novel insights into epigenetic regulation of EAE.",
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AU - Zhong, Jixin

AU - Yu, Qilin

AU - Yang, Ping

AU - Rao, Xiaoquan

AU - He, Long

AU - Fang, Jing

AU - Tu, Yaqin

AU - Zhang, Zhijun

AU - Lai, Qiaohong

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AU - Kuczma, Michal

AU - Kraj, Piatr

AU - Xu, Jun Fa

AU - Gong, Feili

AU - Zhou, Jianfeng

AU - Wen, Li

AU - Eizirik, Decio L.

AU - Du, Jie

AU - Wang, Wei

AU - Wang, Cong Yi

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N2 - Unlike genetic alterations, epigenetic modifications are reversible and amenable to pharmacological interventions, which make them appealing targets for clinical therapy. However, little is known about epigenetic regulation in experimental autoimmune encephalomyelitis (EAE). Here we demonstrated that methyl-CpG-binding domain protein 2 (MBD2), an epigenetic regulator, controls autoimmunity and EAE through T-bet/Hlx. Tbx21 and Hlx underwent a DNA methylation turnover upon polarizations and a unique methylation pattern was essential for T H 17 development. Loss of Mbd2 resulted in a defect for reading the information encoded by this methylation turnover, which disrupted the homeostasis of T-bet/Hlx axis and suppressed T H 17 differentiation. DNA demethylation induced similar effect on helper T cell differentiation. Therefore, Mbd2 -/- mice were completely protected from EAE. Pathogenic splenocytes isolated from wild-type mice challenged with MOG35-55 could adoptively transfer disease to Mbd2 -/- mice. In addition, Mbd2 -/- mice reconstituted with unstimulated wild-type splenocytes developed EAE as wild-type mice did. These data would provide novel insights into epigenetic regulation of EAE.

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