Epigenetics and autoimmunity.
Advances in genetics, such as sequencing of the human genome, have contributed to identification of susceptible genetic patterns in autoimmune diseases (AID). However, genetics is only one aspect of the diseases that does not reflect the influence of environment, sex or aging. Epigenetics, the control of gene packaging and expression independent of alterations in the DNA sequence, is providing new directions linking genetics and environmental factors. Recent findings have contributed to our understanding of how epigenetic modifications could influence AID development, showing differences between AID patients and healthy controls but also showing how one disease differs from another. With regards to epigenetic abnormalities, DNA methylation and histone modifications could be affected leading to large spatial and temporal changes in gene regulation. Other epigenetic processes, such as the influence of the ionic milieu around chromatin and DNA supercoiling stresses may be suspected also. The newly described role of microRNAs in control of gene expression is important by promoting or suppressing autoreactivity in AID. As a consequence control of cellular processes is affected becoming conducive, for example, to the development of autoreactive lymphocytes in systemic lupus erythematosus, synoviocyte proliferation in rheumatoid arthritis, or neural demyelination in multiple sclerosis. Application of epigenetics to AID is in its infancy and requires new hypotheses, techniques, tools, and collaborations between basic epigenetic researchers and autoimmune researchers in order to improve our comprehension of AID. From this will arise new therapeutics, means for early intervention, and perhaps prevention.
Brooks
Wesley H
WH
Experimental HTS, Drug Discovery, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida, USA.
Le Dantec
Christelle
C
Pers
Jacques-Olivier
JO
Youinou
Pierre
P
Renaudineau
Yves
Y
D000818:Animals; D001327:Autoimmune Diseases / Q000209:etiology* / Q000276:immunology / Q000503:physiopathology; D015551:Autoimmunity / Q000235:genetics*; D019175:DNA Methylation / Q000276:immunology; D004781:Environmental Exposure / Q000009:adverse effects*; D044127:Epigenesis, Genetic; D005786:Gene Expression Regulation; D006801:Humans; D056186:Metagenomics; D035683:MicroRNAs
D035683:MicroRNAs