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Altered expression of fragile X mental retardation-1 (FMR1) in the thymus in autoimmune myasthenia gravis

Predisposition to autoimmunity and inflammatory disorders is observed in patients with fragile X-associated syndromes. These patients have increased numbers of CGG triplets in the 5’ UTR region of FMR1 (Fragile X Mental Retardation 1) gene, that affects its expression. FMR1 is decreased in the thymu...

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Autores principales: Thomas, Scott, Fayet, Odessa-Maud, Truffault, Frédérique, Fadel, Elie, Provost, Bastien, Hamza, Abderaouf, Berrih-Aknin, Sonia, Bonnefont, Jean-Paul, Le Panse, Rozen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8597299/
https://www.ncbi.nlm.nih.gov/pubmed/34789272
http://dx.doi.org/10.1186/s12974-021-02311-y
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author Thomas, Scott
Fayet, Odessa-Maud
Truffault, Frédérique
Fadel, Elie
Provost, Bastien
Hamza, Abderaouf
Berrih-Aknin, Sonia
Bonnefont, Jean-Paul
Le Panse, Rozen
author_facet Thomas, Scott
Fayet, Odessa-Maud
Truffault, Frédérique
Fadel, Elie
Provost, Bastien
Hamza, Abderaouf
Berrih-Aknin, Sonia
Bonnefont, Jean-Paul
Le Panse, Rozen
author_sort Thomas, Scott
collection PubMed
description Predisposition to autoimmunity and inflammatory disorders is observed in patients with fragile X-associated syndromes. These patients have increased numbers of CGG triplets in the 5’ UTR region of FMR1 (Fragile X Mental Retardation 1) gene, that affects its expression. FMR1 is decreased in the thymus of myasthenia gravis (MG) patients, a prototypical autoimmune disease. We thus analyzed the number of CGG triplets in FMR1 in MG, and explored the regulatory mechanisms affecting thymic FMR1 expression. We measured the number of CGGs using thymic DNA from MG and controls, but no abnormalities in CGGs were found in MG that could explain thymic decrease of FMR1. We next analyzed by RT-PCR the expression of FMR1 and its transcription factors in thymic samples, and in thymic epithelial cell cultures in response to inflammatory stimuli. In control thymuses, FMR1 expression was higher in males than females, and correlated with CTCF (CCCTC-binding factor) expression. In MG thymuses, decreased expression of FMR1 was correlated with both CTCF and MAX (Myc-associated factor X) expression. Changes in FMR1 expression were supported by western blot analyses for FMRP. In addition, we demonstrated that FMR1, CTCF and MAX expression in thymic epithelial cells was also sensitive to inflammatory signals. Our results suggest that FMR1 could play a central role in the thymus and autoimmunity. First, in relation with the higher susceptibility of females to autoimmune diseases. Second, due to the modulation of its expression by inflammatory signals that are known to be altered in MG thymuses.
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spelling pubmed-85972992021-11-17 Altered expression of fragile X mental retardation-1 (FMR1) in the thymus in autoimmune myasthenia gravis Thomas, Scott Fayet, Odessa-Maud Truffault, Frédérique Fadel, Elie Provost, Bastien Hamza, Abderaouf Berrih-Aknin, Sonia Bonnefont, Jean-Paul Le Panse, Rozen J Neuroinflammation Short Report Predisposition to autoimmunity and inflammatory disorders is observed in patients with fragile X-associated syndromes. These patients have increased numbers of CGG triplets in the 5’ UTR region of FMR1 (Fragile X Mental Retardation 1) gene, that affects its expression. FMR1 is decreased in the thymus of myasthenia gravis (MG) patients, a prototypical autoimmune disease. We thus analyzed the number of CGG triplets in FMR1 in MG, and explored the regulatory mechanisms affecting thymic FMR1 expression. We measured the number of CGGs using thymic DNA from MG and controls, but no abnormalities in CGGs were found in MG that could explain thymic decrease of FMR1. We next analyzed by RT-PCR the expression of FMR1 and its transcription factors in thymic samples, and in thymic epithelial cell cultures in response to inflammatory stimuli. In control thymuses, FMR1 expression was higher in males than females, and correlated with CTCF (CCCTC-binding factor) expression. In MG thymuses, decreased expression of FMR1 was correlated with both CTCF and MAX (Myc-associated factor X) expression. Changes in FMR1 expression were supported by western blot analyses for FMRP. In addition, we demonstrated that FMR1, CTCF and MAX expression in thymic epithelial cells was also sensitive to inflammatory signals. Our results suggest that FMR1 could play a central role in the thymus and autoimmunity. First, in relation with the higher susceptibility of females to autoimmune diseases. Second, due to the modulation of its expression by inflammatory signals that are known to be altered in MG thymuses. BioMed Central 2021-11-17 /pmc/articles/PMC8597299/ /pubmed/34789272 http://dx.doi.org/10.1186/s12974-021-02311-y Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Short Report
Thomas, Scott
Fayet, Odessa-Maud
Truffault, Frédérique
Fadel, Elie
Provost, Bastien
Hamza, Abderaouf
Berrih-Aknin, Sonia
Bonnefont, Jean-Paul
Le Panse, Rozen
Altered expression of fragile X mental retardation-1 (FMR1) in the thymus in autoimmune myasthenia gravis
title Altered expression of fragile X mental retardation-1 (FMR1) in the thymus in autoimmune myasthenia gravis
title_full Altered expression of fragile X mental retardation-1 (FMR1) in the thymus in autoimmune myasthenia gravis
title_fullStr Altered expression of fragile X mental retardation-1 (FMR1) in the thymus in autoimmune myasthenia gravis
title_full_unstemmed Altered expression of fragile X mental retardation-1 (FMR1) in the thymus in autoimmune myasthenia gravis
title_short Altered expression of fragile X mental retardation-1 (FMR1) in the thymus in autoimmune myasthenia gravis
title_sort altered expression of fragile x mental retardation-1 (fmr1) in the thymus in autoimmune myasthenia gravis
topic Short Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8597299/
https://www.ncbi.nlm.nih.gov/pubmed/34789272
http://dx.doi.org/10.1186/s12974-021-02311-y
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