https://www.emjreviews.com/allergy-immuThe 'Nucleolus' Hypothesis of Autoimmune Diseases and Its Implications
Many autoimmune diseases, such as lupus and Sjögren’s syndrome, have a female bias and adult onset. One possible explanation for this bias is disruption of the inactive X chromosome, which is a major epigenetic feature in female cells. Indeed, only one X chromosome is needed in male and female somat...
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doaj-0ce7fab24e4444aca10e27aaf102f4b72020-11-25T03:52:06ZengEuropean Medical JournalEuropean Medical Journal2397-67642017-06-01228289https://www.emjreviews.com/allergy-immuThe 'Nucleolus' Hypothesis of Autoimmune Diseases and Its ImplicationsWesley H. Brooks0Yves Renaudineau1Department of Chemistry, University of South Florida, Tampa, Florida, USAINSERM ESPRI, ERI29/EA2216, LabEx IGO “Immunotherapy Graft Oncology”, Réseau épigénétique et réseau canaux ioniques du Cancéropole Grand Ouest, European University of Brittany, Brest, France; Laboratory of Immunology and Immunotherapy, Brest University Medical School Hôpital, Morvan, Brest, FranceMany autoimmune diseases, such as lupus and Sjögren’s syndrome, have a female bias and adult onset. One possible explanation for this bias is disruption of the inactive X chromosome, which is a major epigenetic feature in female cells. Indeed, only one X chromosome is needed in male and female somatic cells because most X-linked genes are not sex-specific. Therefore, one of the two X chromosomes in each female cell is inactivated and appears as a heterochromatic body near the nuclear membrane. It has also been reported that the inactive X is often in close association with a nucleolus, as if nucleoli help maintain the inactive state. The main function of nucleoli is to assemble ribonucleoprotein complexes (RNPs) such as ribosomal subunits and splicing components. For that purpose, nucleoli have high levels of polyamines which assist with the folding and assembly of RNPs. However, as observed under abnormal circumstances such as cellular stress, the nucleolus is very active and can expand dramatically, potentially engulfing the inactive X, which is sandwiched between the nuclear membrane and the nucleolus. As a consequence, polyamines present in the nucleolus could stabilise autoantigenic complexes including those arising from disruption of the inactive X, or autosomes that contain nucleolar organising regions that keep those chromosomes near nucleoli. This suggests that a variety of seemingly unrelated autoantigens can occur in autoimmune diseases through this scenario. In fact, many autoantigens are, at least transiently, components of the nucleolus. Here, with particular emphasis on the inactive X chromosome, we discuss the ‘nucleolus’ hypothesis in which disruption of chromatin due to abnormal nucleolar exposure can lead to autoimmune diseases.https://www.emjreviews.com/allergy-immunology/article/the-nucleolus-hypothesis-of-autoimmune-diseases-and-its-implications/epigeneticsnucleolusautoimmune diseasesx chromosomepolyamineslupusrheumatoid arthritis (ra)multiple sclerosis (ms)sjögren’s syndrome (sjs) |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Wesley H. Brooks Yves Renaudineau |
spellingShingle |
Wesley H. Brooks Yves Renaudineau https://www.emjreviews.com/allergy-immuThe 'Nucleolus' Hypothesis of Autoimmune Diseases and Its Implications European Medical Journal epigenetics nucleolus autoimmune diseases x chromosome polyamines lupus rheumatoid arthritis (ra) multiple sclerosis (ms) sjögren’s syndrome (sjs) |
author_facet |
Wesley H. Brooks Yves Renaudineau |
author_sort |
Wesley H. Brooks |
title |
https://www.emjreviews.com/allergy-immuThe 'Nucleolus' Hypothesis of Autoimmune Diseases and Its Implications |
title_short |
https://www.emjreviews.com/allergy-immuThe 'Nucleolus' Hypothesis of Autoimmune Diseases and Its Implications |
title_full |
https://www.emjreviews.com/allergy-immuThe 'Nucleolus' Hypothesis of Autoimmune Diseases and Its Implications |
title_fullStr |
https://www.emjreviews.com/allergy-immuThe 'Nucleolus' Hypothesis of Autoimmune Diseases and Its Implications |
title_full_unstemmed |
https://www.emjreviews.com/allergy-immuThe 'Nucleolus' Hypothesis of Autoimmune Diseases and Its Implications |
title_sort |
https://www.emjreviews.com/allergy-immuthe 'nucleolus' hypothesis of autoimmune diseases and its implications |
publisher |
European Medical Journal |
series |
European Medical Journal |
issn |
2397-6764 |
publishDate |
2017-06-01 |
description |
Many autoimmune diseases, such as lupus and Sjögren’s syndrome, have a female bias and adult onset. One possible explanation for this bias is disruption of the inactive X chromosome, which is a major epigenetic feature in female cells. Indeed, only one X chromosome is needed in male and female somatic cells because most X-linked genes are not sex-specific. Therefore, one of the two X chromosomes in each female cell is inactivated and appears as a heterochromatic body near the nuclear membrane. It has also been reported that the inactive X is often in close association with a nucleolus, as if nucleoli help maintain the inactive state. The main function of nucleoli is to assemble ribonucleoprotein complexes (RNPs) such as ribosomal subunits and splicing components. For that purpose, nucleoli have high levels of polyamines which assist with the folding and assembly of RNPs. However, as observed under abnormal circumstances such as cellular stress, the nucleolus is very active and can expand dramatically, potentially engulfing the inactive X, which is sandwiched between the nuclear membrane and the nucleolus. As a consequence, polyamines present in the nucleolus could stabilise autoantigenic complexes including those arising from disruption of the inactive X, or autosomes that contain nucleolar organising regions that keep those chromosomes near nucleoli. This suggests that a variety of seemingly unrelated autoantigens can occur in autoimmune diseases through this scenario. In fact, many autoantigens are, at least transiently, components of the nucleolus. Here, with particular emphasis on the inactive X chromosome, we discuss the ‘nucleolus’ hypothesis in which disruption of chromatin due to abnormal nucleolar exposure can lead to autoimmune diseases. |
topic |
epigenetics nucleolus autoimmune diseases x chromosome polyamines lupus rheumatoid arthritis (ra) multiple sclerosis (ms) sjögren’s syndrome (sjs) |
url |
https://www.emjreviews.com/allergy-immunology/article/the-nucleolus-hypothesis-of-autoimmune-diseases-and-its-implications/ |
work_keys_str_mv |
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