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Aurora A controls CD8(+) T cell cytotoxic activity and antiviral response

Aurora A is a serine/threonine kinase whose role in cell cycle progression and tumour generation has been widely studied. Recent work has revealed an unexpected function for Aurora A during CD4(+) T cell activation and, also, in graft versus host disease development. However, it remains unknown whet...

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Autores principales: Bustos-Morán, Eugenio, Blas-Rus, Noelia, Alcaraz-Serna, Ana, Iborra, Salvador, González-Martínez, José, Malumbres, Marcos, Sánchez-Madrid, Francisco
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6379542/
https://www.ncbi.nlm.nih.gov/pubmed/30778113
http://dx.doi.org/10.1038/s41598-019-38647-y
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author Bustos-Morán, Eugenio
Blas-Rus, Noelia
Alcaraz-Serna, Ana
Iborra, Salvador
González-Martínez, José
Malumbres, Marcos
Sánchez-Madrid, Francisco
author_facet Bustos-Morán, Eugenio
Blas-Rus, Noelia
Alcaraz-Serna, Ana
Iborra, Salvador
González-Martínez, José
Malumbres, Marcos
Sánchez-Madrid, Francisco
author_sort Bustos-Morán, Eugenio
collection PubMed
description Aurora A is a serine/threonine kinase whose role in cell cycle progression and tumour generation has been widely studied. Recent work has revealed an unexpected function for Aurora A during CD4(+) T cell activation and, also, in graft versus host disease development. However, it remains unknown whether Aurora A is involved in CD8(+) T cell effector function and in cytotoxic T lymphocyte-mediated antiviral response. Here, we show that Aurora A chemical inhibition leads to an impairment of both the peptide-specific cytotoxicity and the degranulation activity of CD8(+) T cells. This finding was similarly proven for both mice and human CD8(+) CTL activity. As a result of Aurora A blockade, we detected a reduction in the expression induced by T cell activation of genes classically related to the effector function of cytotoxic T lymphocytes such as granzyme B or perforin1. Finally, we have found that Aurora A is necessary for CD8(+) T cell-mediated antiviral response, in an in vivo model of vaccinia virus infection. Thus, we can conclude that Aurora A activity is, indeed, needed for the proper effector function of cytotoxic T lymphocytes and for their activity against viral threats.
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spelling pubmed-63795422019-02-21 Aurora A controls CD8(+) T cell cytotoxic activity and antiviral response Bustos-Morán, Eugenio Blas-Rus, Noelia Alcaraz-Serna, Ana Iborra, Salvador González-Martínez, José Malumbres, Marcos Sánchez-Madrid, Francisco Sci Rep Article Aurora A is a serine/threonine kinase whose role in cell cycle progression and tumour generation has been widely studied. Recent work has revealed an unexpected function for Aurora A during CD4(+) T cell activation and, also, in graft versus host disease development. However, it remains unknown whether Aurora A is involved in CD8(+) T cell effector function and in cytotoxic T lymphocyte-mediated antiviral response. Here, we show that Aurora A chemical inhibition leads to an impairment of both the peptide-specific cytotoxicity and the degranulation activity of CD8(+) T cells. This finding was similarly proven for both mice and human CD8(+) CTL activity. As a result of Aurora A blockade, we detected a reduction in the expression induced by T cell activation of genes classically related to the effector function of cytotoxic T lymphocytes such as granzyme B or perforin1. Finally, we have found that Aurora A is necessary for CD8(+) T cell-mediated antiviral response, in an in vivo model of vaccinia virus infection. Thus, we can conclude that Aurora A activity is, indeed, needed for the proper effector function of cytotoxic T lymphocytes and for their activity against viral threats. Nature Publishing Group UK 2019-02-18 /pmc/articles/PMC6379542/ /pubmed/30778113 http://dx.doi.org/10.1038/s41598-019-38647-y Text en © The Author(s) 2019 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
Bustos-Morán, Eugenio
Blas-Rus, Noelia
Alcaraz-Serna, Ana
Iborra, Salvador
González-Martínez, José
Malumbres, Marcos
Sánchez-Madrid, Francisco
Aurora A controls CD8(+) T cell cytotoxic activity and antiviral response
title Aurora A controls CD8(+) T cell cytotoxic activity and antiviral response
title_full Aurora A controls CD8(+) T cell cytotoxic activity and antiviral response
title_fullStr Aurora A controls CD8(+) T cell cytotoxic activity and antiviral response
title_full_unstemmed Aurora A controls CD8(+) T cell cytotoxic activity and antiviral response
title_short Aurora A controls CD8(+) T cell cytotoxic activity and antiviral response
title_sort aurora a controls cd8(+) t cell cytotoxic activity and antiviral response
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6379542/
https://www.ncbi.nlm.nih.gov/pubmed/30778113
http://dx.doi.org/10.1038/s41598-019-38647-y
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