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Interleukin 4 modulates microglia homeostasis and attenuates the early slowly progressive phase of amyotrophic lateral sclerosis
Microglia activation is a commonly pathological hallmark of neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS), a devastating disorder characterized by a selective motor neurons degeneration. Whether such activation might represent a causal event rather than a secondary epipheno...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5833860/ https://www.ncbi.nlm.nih.gov/pubmed/29445154 http://dx.doi.org/10.1038/s41419-018-0288-4 |
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author | Rossi, Chiara Cusimano, Melania Zambito, Martina Finardi, Annamaria Capotondo, Alessia Garcia-Manteiga, Jose Manuel Comi, Giancarlo Furlan, Roberto Martino, Gianvito Muzio, Luca |
author_facet | Rossi, Chiara Cusimano, Melania Zambito, Martina Finardi, Annamaria Capotondo, Alessia Garcia-Manteiga, Jose Manuel Comi, Giancarlo Furlan, Roberto Martino, Gianvito Muzio, Luca |
author_sort | Rossi, Chiara |
collection | PubMed |
description | Microglia activation is a commonly pathological hallmark of neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS), a devastating disorder characterized by a selective motor neurons degeneration. Whether such activation might represent a causal event rather than a secondary epiphenomenon remains elusive. Here, we show that CNS-delivery of IL-4—via a lentiviral-mediated gene therapy strategy—skews microglia to proliferate, inducing these cells to adopt the phenotype of slowly proliferating cells. Transcriptome analysis revealed that IL-4-treated microglia express a broad number of genes normally encoded by embryonic microglia. Since embryonic microglia sustain CNS development, we then hypothesized that turning adult microglia to acquire such phenotype via IL-4 might be an efficient in vivo strategy to sustain motor neuron survival in ALS. IL-4 gene therapy in SOD1(G93A) mice resulted in a general amelioration of clinical outcomes during the early slowly progressive phase of the disease. However, such approach did not revert neurodegenerative processes occurring in the late and fast progressing phase of the disease. |
format | Online Article Text |
id | pubmed-5833860 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-58338602018-03-06 Interleukin 4 modulates microglia homeostasis and attenuates the early slowly progressive phase of amyotrophic lateral sclerosis Rossi, Chiara Cusimano, Melania Zambito, Martina Finardi, Annamaria Capotondo, Alessia Garcia-Manteiga, Jose Manuel Comi, Giancarlo Furlan, Roberto Martino, Gianvito Muzio, Luca Cell Death Dis Article Microglia activation is a commonly pathological hallmark of neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS), a devastating disorder characterized by a selective motor neurons degeneration. Whether such activation might represent a causal event rather than a secondary epiphenomenon remains elusive. Here, we show that CNS-delivery of IL-4—via a lentiviral-mediated gene therapy strategy—skews microglia to proliferate, inducing these cells to adopt the phenotype of slowly proliferating cells. Transcriptome analysis revealed that IL-4-treated microglia express a broad number of genes normally encoded by embryonic microglia. Since embryonic microglia sustain CNS development, we then hypothesized that turning adult microglia to acquire such phenotype via IL-4 might be an efficient in vivo strategy to sustain motor neuron survival in ALS. IL-4 gene therapy in SOD1(G93A) mice resulted in a general amelioration of clinical outcomes during the early slowly progressive phase of the disease. However, such approach did not revert neurodegenerative processes occurring in the late and fast progressing phase of the disease. Nature Publishing Group UK 2018-02-14 /pmc/articles/PMC5833860/ /pubmed/29445154 http://dx.doi.org/10.1038/s41419-018-0288-4 Text en © The Author(s) 2018 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 Rossi, Chiara Cusimano, Melania Zambito, Martina Finardi, Annamaria Capotondo, Alessia Garcia-Manteiga, Jose Manuel Comi, Giancarlo Furlan, Roberto Martino, Gianvito Muzio, Luca Interleukin 4 modulates microglia homeostasis and attenuates the early slowly progressive phase of amyotrophic lateral sclerosis |
title | Interleukin 4 modulates microglia homeostasis and attenuates the early slowly progressive phase of amyotrophic lateral sclerosis |
title_full | Interleukin 4 modulates microglia homeostasis and attenuates the early slowly progressive phase of amyotrophic lateral sclerosis |
title_fullStr | Interleukin 4 modulates microglia homeostasis and attenuates the early slowly progressive phase of amyotrophic lateral sclerosis |
title_full_unstemmed | Interleukin 4 modulates microglia homeostasis and attenuates the early slowly progressive phase of amyotrophic lateral sclerosis |
title_short | Interleukin 4 modulates microglia homeostasis and attenuates the early slowly progressive phase of amyotrophic lateral sclerosis |
title_sort | interleukin 4 modulates microglia homeostasis and attenuates the early slowly progressive phase of amyotrophic lateral sclerosis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5833860/ https://www.ncbi.nlm.nih.gov/pubmed/29445154 http://dx.doi.org/10.1038/s41419-018-0288-4 |
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