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

Abstract 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...

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Autores principales:	Scott Thomas, Odessa-Maud Fayet, Frédérique Truffault, Elie Fadel, Bastien Provost, Abderaouf Hamza, Sonia Berrih-Aknin, Jean-Paul Bonnefont, Rozen Le Panse
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Fragile X syndromes Autoimmunity FMR1 Thymus Myasthenia gravis Inflammatory cytokines Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/9deab7876400409a9bac10a74b0c4241
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spelling	oai:doaj.org-article:9deab7876400409a9bac10a74b0c42412021-11-21T12:39:52ZAltered expression of fragile X mental retardation-1 (FMR1) in the thymus in autoimmune myasthenia gravis10.1186/s12974-021-02311-y1742-2094https://doaj.org/article/9deab7876400409a9bac10a74b0c42412021-11-01T00:00:00Zhttps://doi.org/10.1186/s12974-021-02311-yhttps://doaj.org/toc/1742-2094Abstract 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.Scott ThomasOdessa-Maud FayetFrédérique TruffaultElie FadelBastien ProvostAbderaouf HamzaSonia Berrih-AkninJean-Paul BonnefontRozen Le PanseBMCarticleFragile X syndromesAutoimmunityFMR1ThymusMyasthenia gravisInflammatory cytokinesNeurology. Diseases of the nervous systemRC346-429ENJournal of Neuroinflammation, Vol 18, Iss 1, Pp 1-8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Fragile X syndromes Autoimmunity FMR1 Thymus Myasthenia gravis Inflammatory cytokines Neurology. Diseases of the nervous system RC346-429
spellingShingle	Fragile X syndromes Autoimmunity FMR1 Thymus Myasthenia gravis Inflammatory cytokines Neurology. Diseases of the nervous system RC346-429 Scott Thomas Odessa-Maud Fayet Frédérique Truffault Elie Fadel Bastien Provost Abderaouf Hamza Sonia Berrih-Aknin Jean-Paul Bonnefont Rozen Le Panse Altered expression of fragile X mental retardation-1 (FMR1) in the thymus in autoimmune myasthenia gravis
description	Abstract 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.
format	article
author	Scott Thomas Odessa-Maud Fayet Frédérique Truffault Elie Fadel Bastien Provost Abderaouf Hamza Sonia Berrih-Aknin Jean-Paul Bonnefont Rozen Le Panse
author_facet	Scott Thomas Odessa-Maud Fayet Frédérique Truffault Elie Fadel Bastien Provost Abderaouf Hamza Sonia Berrih-Aknin Jean-Paul Bonnefont Rozen Le Panse
author_sort	Scott Thomas
title	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_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_sort	altered expression of fragile x mental retardation-1 (fmr1) in the thymus in autoimmune myasthenia gravis
publisher	BMC
publishDate	2021
url	https://doaj.org/article/9deab7876400409a9bac10a74b0c4241
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Altered expression of fragile X mental retardation-1 (FMR1) in the thymus in autoimmune myasthenia gravis

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