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Toll-like receptor 4 modulation influences human neural stem cell proliferation and differentiation
Toll-like receptor 4 (TLR4) activation is pivotal to innate immunity and has been shown to regulate proliferation and differentiation of human neural stem cells (hNSCs) in vivo. Here we study the role of TLR4 in regulating hNSC derived from the human telencephalic-diencephalic area of the fetal brai...
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/PMC5833460/ https://www.ncbi.nlm.nih.gov/pubmed/29449625 http://dx.doi.org/10.1038/s41419-017-0139-8 |
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author | Grasselli, Chiara Ferrari, Daniela Zalfa, Cristina Soncini, Matias Mazzoccoli, Gianluigi Facchini, Fabio A. Marongiu, Laura Granucci, Francesca Copetti, Massimiliano Vescovi, Angelo Luigi Peri, Francesco De Filippis, Lidia |
author_facet | Grasselli, Chiara Ferrari, Daniela Zalfa, Cristina Soncini, Matias Mazzoccoli, Gianluigi Facchini, Fabio A. Marongiu, Laura Granucci, Francesca Copetti, Massimiliano Vescovi, Angelo Luigi Peri, Francesco De Filippis, Lidia |
author_sort | Grasselli, Chiara |
collection | PubMed |
description | Toll-like receptor 4 (TLR4) activation is pivotal to innate immunity and has been shown to regulate proliferation and differentiation of human neural stem cells (hNSCs) in vivo. Here we study the role of TLR4 in regulating hNSC derived from the human telencephalic-diencephalic area of the fetal brain and cultured in vitro as neurospheres in compliance with Good Manifacture Procedures (GMP) guidelines. Similar batches have been used in recent clinical trials in ALS patients. We found that TLR2 and 4 are expressed in hNSCs as well as CD14 and MD-2 co-receptors, and TLR4 expression is downregulated upon differentiation. Activation of TLR4 signaling by lipopolysaccharide (LPS) has a positive effect on proliferation and/or survival while the inverse is observed with TLR4 inhibition by a synthetic antagonist. TLR4 activation promotes neuronal and oligodendrocyte differentiation and/or survival while TLR4 inhibition leads to increased apoptosis. Consistently, endogenous expression of TLR4 is retained by hNSC surviving after transplantation in ALS rats or immunocompromised mice, thus irrespectively of the neuroinflammatory environment. The characterization of downstream signaling of TLR4 in hNSCs has suggested some activation of the inflammasome pathway. This study suggests TLR4 signaling as essential for hNSC self-renewal and as a novel target for the study of neurogenetic mechanisms. |
format | Online Article Text |
id | pubmed-5833460 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-58334602018-03-06 Toll-like receptor 4 modulation influences human neural stem cell proliferation and differentiation Grasselli, Chiara Ferrari, Daniela Zalfa, Cristina Soncini, Matias Mazzoccoli, Gianluigi Facchini, Fabio A. Marongiu, Laura Granucci, Francesca Copetti, Massimiliano Vescovi, Angelo Luigi Peri, Francesco De Filippis, Lidia Cell Death Dis Article Toll-like receptor 4 (TLR4) activation is pivotal to innate immunity and has been shown to regulate proliferation and differentiation of human neural stem cells (hNSCs) in vivo. Here we study the role of TLR4 in regulating hNSC derived from the human telencephalic-diencephalic area of the fetal brain and cultured in vitro as neurospheres in compliance with Good Manifacture Procedures (GMP) guidelines. Similar batches have been used in recent clinical trials in ALS patients. We found that TLR2 and 4 are expressed in hNSCs as well as CD14 and MD-2 co-receptors, and TLR4 expression is downregulated upon differentiation. Activation of TLR4 signaling by lipopolysaccharide (LPS) has a positive effect on proliferation and/or survival while the inverse is observed with TLR4 inhibition by a synthetic antagonist. TLR4 activation promotes neuronal and oligodendrocyte differentiation and/or survival while TLR4 inhibition leads to increased apoptosis. Consistently, endogenous expression of TLR4 is retained by hNSC surviving after transplantation in ALS rats or immunocompromised mice, thus irrespectively of the neuroinflammatory environment. The characterization of downstream signaling of TLR4 in hNSCs has suggested some activation of the inflammasome pathway. This study suggests TLR4 signaling as essential for hNSC self-renewal and as a novel target for the study of neurogenetic mechanisms. Nature Publishing Group UK 2018-02-15 /pmc/articles/PMC5833460/ /pubmed/29449625 http://dx.doi.org/10.1038/s41419-017-0139-8 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 Grasselli, Chiara Ferrari, Daniela Zalfa, Cristina Soncini, Matias Mazzoccoli, Gianluigi Facchini, Fabio A. Marongiu, Laura Granucci, Francesca Copetti, Massimiliano Vescovi, Angelo Luigi Peri, Francesco De Filippis, Lidia Toll-like receptor 4 modulation influences human neural stem cell proliferation and differentiation |
title | Toll-like receptor 4 modulation influences human neural stem cell proliferation and differentiation |
title_full | Toll-like receptor 4 modulation influences human neural stem cell proliferation and differentiation |
title_fullStr | Toll-like receptor 4 modulation influences human neural stem cell proliferation and differentiation |
title_full_unstemmed | Toll-like receptor 4 modulation influences human neural stem cell proliferation and differentiation |
title_short | Toll-like receptor 4 modulation influences human neural stem cell proliferation and differentiation |
title_sort | toll-like receptor 4 modulation influences human neural stem cell proliferation and differentiation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5833460/ https://www.ncbi.nlm.nih.gov/pubmed/29449625 http://dx.doi.org/10.1038/s41419-017-0139-8 |
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