Transcriptional dysregulation of Interferome in experimental and human Multiple Sclerosis

Abstract Recent evidence indicates that single multiple sclerosis (MS) susceptibility genes involved in interferon (IFN) signaling display altered transcript levels in peripheral blood of untreated MS subjects, suggesting that responsiveness to endogenous IFN is dysregulated during neuroinflammation...

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Autores principales:	Sundararajan Srinivasan, Martina Severa, Fabiana Rizzo, Ramesh Menon, Elena Brini, Rosella Mechelli, Vittorio Martinelli, Paul Hertzog, Marco Salvetti, Roberto Furlan, Gianvito Martino, Giancarlo Comi, Eliana M. Coccia, Cinthia Farina
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5eca37b29ea3460fbd37602ded3bbfa2
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spelling	oai:doaj.org-article:5eca37b29ea3460fbd37602ded3bbfa22021-12-02T15:05:09ZTranscriptional dysregulation of Interferome in experimental and human Multiple Sclerosis10.1038/s41598-017-09286-y2045-2322https://doaj.org/article/5eca37b29ea3460fbd37602ded3bbfa22017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-09286-yhttps://doaj.org/toc/2045-2322Abstract Recent evidence indicates that single multiple sclerosis (MS) susceptibility genes involved in interferon (IFN) signaling display altered transcript levels in peripheral blood of untreated MS subjects, suggesting that responsiveness to endogenous IFN is dysregulated during neuroinflammation. To prove this hypothesis we exploited the systematic collection of IFN regulated genes (IRG) provided by the Interferome database and mapped Interferome changes in experimental and human MS. Indeed, central nervous system tissue and encephalitogenic CD4 T cells during experimental autoimmune encephalomyelitis were characterized by massive changes in Interferome transcription. Further, the analysis of almost 500 human blood transcriptomes showed that (i) several IRG changed expression at distinct MS stages with a core of 21 transcripts concordantly dysregulated in all MS forms compared with healthy subjects; (ii) 100 differentially expressed IRG were validated in independent case-control cohorts; and (iii) 53 out of 100 dysregulated IRG were targeted by IFN-beta treatment in vivo. Finally, ex vivo and in vitro experiments established that IFN-beta administration modulated expression of two IRG, ARRB1 and CHP1, in immune cells. Our study confirms the impairment of Interferome in experimental and human MS, and describes IRG signatures at distinct disease stages which can represent novel therapeutic targets in MS.Sundararajan SrinivasanMartina SeveraFabiana RizzoRamesh MenonElena BriniRosella MechelliVittorio MartinelliPaul HertzogMarco SalvettiRoberto FurlanGianvito MartinoGiancarlo ComiEliana M. CocciaCinthia FarinaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-9 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sundararajan Srinivasan Martina Severa Fabiana Rizzo Ramesh Menon Elena Brini Rosella Mechelli Vittorio Martinelli Paul Hertzog Marco Salvetti Roberto Furlan Gianvito Martino Giancarlo Comi Eliana M. Coccia Cinthia Farina Transcriptional dysregulation of Interferome in experimental and human Multiple Sclerosis
description	Abstract Recent evidence indicates that single multiple sclerosis (MS) susceptibility genes involved in interferon (IFN) signaling display altered transcript levels in peripheral blood of untreated MS subjects, suggesting that responsiveness to endogenous IFN is dysregulated during neuroinflammation. To prove this hypothesis we exploited the systematic collection of IFN regulated genes (IRG) provided by the Interferome database and mapped Interferome changes in experimental and human MS. Indeed, central nervous system tissue and encephalitogenic CD4 T cells during experimental autoimmune encephalomyelitis were characterized by massive changes in Interferome transcription. Further, the analysis of almost 500 human blood transcriptomes showed that (i) several IRG changed expression at distinct MS stages with a core of 21 transcripts concordantly dysregulated in all MS forms compared with healthy subjects; (ii) 100 differentially expressed IRG were validated in independent case-control cohorts; and (iii) 53 out of 100 dysregulated IRG were targeted by IFN-beta treatment in vivo. Finally, ex vivo and in vitro experiments established that IFN-beta administration modulated expression of two IRG, ARRB1 and CHP1, in immune cells. Our study confirms the impairment of Interferome in experimental and human MS, and describes IRG signatures at distinct disease stages which can represent novel therapeutic targets in MS.
format	article
author	Sundararajan Srinivasan Martina Severa Fabiana Rizzo Ramesh Menon Elena Brini Rosella Mechelli Vittorio Martinelli Paul Hertzog Marco Salvetti Roberto Furlan Gianvito Martino Giancarlo Comi Eliana M. Coccia Cinthia Farina
author_facet	Sundararajan Srinivasan Martina Severa Fabiana Rizzo Ramesh Menon Elena Brini Rosella Mechelli Vittorio Martinelli Paul Hertzog Marco Salvetti Roberto Furlan Gianvito Martino Giancarlo Comi Eliana M. Coccia Cinthia Farina
author_sort	Sundararajan Srinivasan
title	Transcriptional dysregulation of Interferome in experimental and human Multiple Sclerosis
title_short	Transcriptional dysregulation of Interferome in experimental and human Multiple Sclerosis
title_full	Transcriptional dysregulation of Interferome in experimental and human Multiple Sclerosis
title_fullStr	Transcriptional dysregulation of Interferome in experimental and human Multiple Sclerosis
title_full_unstemmed	Transcriptional dysregulation of Interferome in experimental and human Multiple Sclerosis
title_sort	transcriptional dysregulation of interferome in experimental and human multiple sclerosis
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/5eca37b29ea3460fbd37602ded3bbfa2
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Transcriptional dysregulation of Interferome in experimental and human Multiple Sclerosis

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