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Mosaicism of XX and XXY cells accounts for high copy number of Toll like Receptor 7 and8 genes in peripheral blood of men with Rheumatoid Arthritis
The X chromosome, hemizygous in males, contains numerous genes important to immunological and hormonal function. Alterations in X-linked gene dosage are suspected to contribute to female predominance in autoimmunity. A powerful example of X-linked dosage involvement comes from the BXSB murine lupus...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6733859/ https://www.ncbi.nlm.nih.gov/pubmed/31501466 http://dx.doi.org/10.1038/s41598-019-49309-4 |
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author | Martin, Gabriel V. Kanaan, Sami B. Hemon, Marie F. Azzouz, Doua F. El Haddad, Marina Balandraud, Nathalie Mignon-Ravix, Cécile Picard, Christophe Arnoux, Fanny Martin, Marielle Roudier, Jean Auger, Isabelle Lambert, Nathalie C. |
author_facet | Martin, Gabriel V. Kanaan, Sami B. Hemon, Marie F. Azzouz, Doua F. El Haddad, Marina Balandraud, Nathalie Mignon-Ravix, Cécile Picard, Christophe Arnoux, Fanny Martin, Marielle Roudier, Jean Auger, Isabelle Lambert, Nathalie C. |
author_sort | Martin, Gabriel V. |
collection | PubMed |
description | The X chromosome, hemizygous in males, contains numerous genes important to immunological and hormonal function. Alterations in X-linked gene dosage are suspected to contribute to female predominance in autoimmunity. A powerful example of X-linked dosage involvement comes from the BXSB murine lupus model, where the duplication of the X-linked Toll-Like Receptor 7 (Tlr7) gene aggravates autoimmunity in male mice. Such alterations are possible in men with autoimmune diseases. Here we showed that a quarter to a third of men with rheumatoid arthritis (RA) had significantly increased copy numbers (CN) of TLR7 gene and its paralog TLR8. Patients with high CN had an upregulated pro-inflammatory JNK/p38 signaling pathway. By fluorescence in situ hybridization, we further demonstrated that the increase in X-linked genes CN was due to the presence of an extra X chromosome in some cells. Men with RA had a significant cellular mosaicism of female (46,XX) and/or Klinefelter (47,XXY) cells among male (46,XY) cells, reaching up to 1.4% in peripheral blood. Our results present a new potential trigger for RA in men and opens a new field of investigation particularly relevant for gender-biased autoimmune diseases. |
format | Online Article Text |
id | pubmed-6733859 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-67338592019-09-20 Mosaicism of XX and XXY cells accounts for high copy number of Toll like Receptor 7 and8 genes in peripheral blood of men with Rheumatoid Arthritis Martin, Gabriel V. Kanaan, Sami B. Hemon, Marie F. Azzouz, Doua F. El Haddad, Marina Balandraud, Nathalie Mignon-Ravix, Cécile Picard, Christophe Arnoux, Fanny Martin, Marielle Roudier, Jean Auger, Isabelle Lambert, Nathalie C. Sci Rep Article The X chromosome, hemizygous in males, contains numerous genes important to immunological and hormonal function. Alterations in X-linked gene dosage are suspected to contribute to female predominance in autoimmunity. A powerful example of X-linked dosage involvement comes from the BXSB murine lupus model, where the duplication of the X-linked Toll-Like Receptor 7 (Tlr7) gene aggravates autoimmunity in male mice. Such alterations are possible in men with autoimmune diseases. Here we showed that a quarter to a third of men with rheumatoid arthritis (RA) had significantly increased copy numbers (CN) of TLR7 gene and its paralog TLR8. Patients with high CN had an upregulated pro-inflammatory JNK/p38 signaling pathway. By fluorescence in situ hybridization, we further demonstrated that the increase in X-linked genes CN was due to the presence of an extra X chromosome in some cells. Men with RA had a significant cellular mosaicism of female (46,XX) and/or Klinefelter (47,XXY) cells among male (46,XY) cells, reaching up to 1.4% in peripheral blood. Our results present a new potential trigger for RA in men and opens a new field of investigation particularly relevant for gender-biased autoimmune diseases. Nature Publishing Group UK 2019-09-09 /pmc/articles/PMC6733859/ /pubmed/31501466 http://dx.doi.org/10.1038/s41598-019-49309-4 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Martin, Gabriel V. Kanaan, Sami B. Hemon, Marie F. Azzouz, Doua F. El Haddad, Marina Balandraud, Nathalie Mignon-Ravix, Cécile Picard, Christophe Arnoux, Fanny Martin, Marielle Roudier, Jean Auger, Isabelle Lambert, Nathalie C. Mosaicism of XX and XXY cells accounts for high copy number of Toll like Receptor 7 and8 genes in peripheral blood of men with Rheumatoid Arthritis |
title | Mosaicism of XX and XXY cells accounts for high copy number of Toll like Receptor 7 and8 genes in peripheral blood of men with Rheumatoid Arthritis |
title_full | Mosaicism of XX and XXY cells accounts for high copy number of Toll like Receptor 7 and8 genes in peripheral blood of men with Rheumatoid Arthritis |
title_fullStr | Mosaicism of XX and XXY cells accounts for high copy number of Toll like Receptor 7 and8 genes in peripheral blood of men with Rheumatoid Arthritis |
title_full_unstemmed | Mosaicism of XX and XXY cells accounts for high copy number of Toll like Receptor 7 and8 genes in peripheral blood of men with Rheumatoid Arthritis |
title_short | Mosaicism of XX and XXY cells accounts for high copy number of Toll like Receptor 7 and8 genes in peripheral blood of men with Rheumatoid Arthritis |
title_sort | mosaicism of xx and xxy cells accounts for high copy number of toll like receptor 7 and8 genes in peripheral blood of men with rheumatoid arthritis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6733859/ https://www.ncbi.nlm.nih.gov/pubmed/31501466 http://dx.doi.org/10.1038/s41598-019-49309-4 |
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