Epigenetics and autoimmunity, with special emphasis on methylation.

Abstract : Epigenetics signifies stable and heritable changes in gene expression without changes in the genetic code. There is a wealth of emerging evidence for such processes in promoting autoimmunity. The first clue is that inhibition of DNA methyl transferases (DNMTs) induces systemic lupus erythematosus (SLE) in animals. Similar immune-mediated disorders have been generated by injecting normal T cells incubated with DNMT inhibitors into healthy mice. Further, monozygotic twins display differences in DNA methylation that parallel discordances in SLE. Moreover, defects in DNA methylation characterize lymphocytes from SLE, synoviocytes from rheumatoid arthritis, and neural cells from multiple sclerosis patients. It has also been shown that DNA hypomethylation of T and B cells correlates with reduced DNMT efficacy and histone acetylation in SLE. Once a gene promoter has been demethylated, the gene recovers its capacity to be transcribed, e.g., genes for cytokines, activation receptors on cells, and endogenous retroviruses. This outcome has been associated with a blockage of the Erk pathway and/or a growth arrest at the G0/G1 interface of the cell cycle. Of importance is the fact that these changes can be reversed. For example, blockade of the interleukin-6 autocrine loop in SLE B cells restores DNA methylation status, thus opening new perspectives for therapy.
Type de document :
Article dans une revue
Keio journal of medicine, School of Medicine Keio University, 2011, 60 (1), pp.10-6
Liste complète des métadonnées

http://hal.univ-brest.fr/hal-00771236
Contributeur : Geneviève Michel <>
Soumis le : mardi 8 janvier 2013 - 11:36:34
Dernière modification le : mercredi 29 novembre 2017 - 14:53:51

Identifiants

  • HAL Id : hal-00771236, version 1
  • PUBMED : 21460598

Collections

Citation

Yves Renaudineau, Pierre Youinou. Epigenetics and autoimmunity, with special emphasis on methylation.. Keio journal of medicine, School of Medicine Keio University, 2011, 60 (1), pp.10-6. 〈hal-00771236〉

Partager

Métriques

Consultations de la notice

87