MeCP2 deficiency exacerbates the neuroinflammatory setting and autoreactive response during an autoimmune challenge

Abstract Rett syndrome is a severe and progressive neurological disorder linked to mutations in the MeCP2 gene. It has been suggested that immune alterations may play an active role in the generation and/or maintenance of RTT phenotypes. However, there is no clear consensus about which pathways are...

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Autores principales:	M. I. Zalosnik, M. C. Fabio, M. L. Bertoldi, C. N. Castañares, A. L. Degano
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e167572fef6d48aba42e87b6f968b708
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spelling	oai:doaj.org-article:e167572fef6d48aba42e87b6f968b7082021-12-02T14:42:20ZMeCP2 deficiency exacerbates the neuroinflammatory setting and autoreactive response during an autoimmune challenge10.1038/s41598-021-90517-82045-2322https://doaj.org/article/e167572fef6d48aba42e87b6f968b7082021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-90517-8https://doaj.org/toc/2045-2322Abstract Rett syndrome is a severe and progressive neurological disorder linked to mutations in the MeCP2 gene. It has been suggested that immune alterations may play an active role in the generation and/or maintenance of RTT phenotypes. However, there is no clear consensus about which pathways are regulated in vivo by MeCP2 in the context of immune activation. In the present work we set to characterize the role of MeCP2 during the progression of Experimental Autoimmune Encephalomyelitis (EAE) using the MeCP2308/y mouse model (MUT), which represents a condition of “MeCP2 function deficiency”. Our results showed that MeCP2 deficiency increased the susceptibility to develop EAE, along with a defective induction of anti-inflammatory responses and an exacerbated MOG-specific IFNγ expression in immune sites. In MUT-EAE spinal cord, we found a chronic increase in pro-inflammatory cytokines gene expression (IFNγ, TNFα and IL-1β) and downregulation of genes involved in immune regulation (IL-10, FoxP3 and CX3CR1). Moreover, our results indicate that MeCP2 acts intrinsically upon immune activation, affecting neuroimmune homeostasis by regulating the pro-inflammatory/anti-inflammatory balance in vivo. These results are relevant to identify the potential consequences of MeCP2 mutations on immune homeostasis and to explore novel therapeutic strategies for MeCP2-related disorders.M. I. ZalosnikM. C. FabioM. L. BertoldiC. N. CastañaresA. L. DeganoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q M. I. Zalosnik M. C. Fabio M. L. Bertoldi C. N. Castañares A. L. Degano MeCP2 deficiency exacerbates the neuroinflammatory setting and autoreactive response during an autoimmune challenge
description	Abstract Rett syndrome is a severe and progressive neurological disorder linked to mutations in the MeCP2 gene. It has been suggested that immune alterations may play an active role in the generation and/or maintenance of RTT phenotypes. However, there is no clear consensus about which pathways are regulated in vivo by MeCP2 in the context of immune activation. In the present work we set to characterize the role of MeCP2 during the progression of Experimental Autoimmune Encephalomyelitis (EAE) using the MeCP2308/y mouse model (MUT), which represents a condition of “MeCP2 function deficiency”. Our results showed that MeCP2 deficiency increased the susceptibility to develop EAE, along with a defective induction of anti-inflammatory responses and an exacerbated MOG-specific IFNγ expression in immune sites. In MUT-EAE spinal cord, we found a chronic increase in pro-inflammatory cytokines gene expression (IFNγ, TNFα and IL-1β) and downregulation of genes involved in immune regulation (IL-10, FoxP3 and CX3CR1). Moreover, our results indicate that MeCP2 acts intrinsically upon immune activation, affecting neuroimmune homeostasis by regulating the pro-inflammatory/anti-inflammatory balance in vivo. These results are relevant to identify the potential consequences of MeCP2 mutations on immune homeostasis and to explore novel therapeutic strategies for MeCP2-related disorders.
format	article
author	M. I. Zalosnik M. C. Fabio M. L. Bertoldi C. N. Castañares A. L. Degano
author_facet	M. I. Zalosnik M. C. Fabio M. L. Bertoldi C. N. Castañares A. L. Degano
author_sort	M. I. Zalosnik
title	MeCP2 deficiency exacerbates the neuroinflammatory setting and autoreactive response during an autoimmune challenge
title_short	MeCP2 deficiency exacerbates the neuroinflammatory setting and autoreactive response during an autoimmune challenge
title_full	MeCP2 deficiency exacerbates the neuroinflammatory setting and autoreactive response during an autoimmune challenge
title_fullStr	MeCP2 deficiency exacerbates the neuroinflammatory setting and autoreactive response during an autoimmune challenge
title_full_unstemmed	MeCP2 deficiency exacerbates the neuroinflammatory setting and autoreactive response during an autoimmune challenge
title_sort	mecp2 deficiency exacerbates the neuroinflammatory setting and autoreactive response during an autoimmune challenge
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/e167572fef6d48aba42e87b6f968b708
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MeCP2 deficiency exacerbates the neuroinflammatory setting and autoreactive response during an autoimmune challenge

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