Context-dependent regulation of Th17-associated genes and IFNγ expression by the transcription factor NFAT5

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• dc.contributor.author Alberdi Ibarzabal, Maria, 1986-ca
• dc.contributor.author Iglesias, Marcosca
• dc.contributor.author Tejedor Vaquero, Sonia, 1988-ca
• dc.contributor.author Merino, Ramónca
• dc.contributor.author López Rodríguez, M. Cristinaca
• dc.contributor.author Aramburu, José (Aramburu Beltrán)ca
• dc.date.accessioned 2017-03-20T13:56:23Z
• dc.date.available 2017-03-20T13:56:23Z
• dc.date.issued 2017
• dc.description.abstract Stress-activated transcription factors influence T-cell function in different physiopathologic contexts. NFAT5, a relative of nuclear factor κB and the calcineurin-activated NFATc transcription factors, protects mammalian cells from hyperosmotic stress caused by the elevation of extracellular sodium levels. In T cells exposed to hypernatremia, NFAT5 not only induces osmoprotective gene products but also cytokines and immune receptors, which raises the question of whether this factor could regulate other T-cell functions in osmostress-independent contexts. Here we have used mice with a conditional deletion of Nfat5 in mature T lymphocytes to explore osmostress-dependent and -independent functions of this factor. In vitro experiments with CD4 T cells stimulated in hyperosmotic medium showed that NFAT5 enhanced the expression of IL-2 and the Th17-associated gene products RORγt and IL-23R. By contrast, NFAT5-deficient CD4 T cells activated in vivo by anti-CD3 antibody exhibited a different activation profile and were skewed towards enhanced interferon γ (IFNγ) and IL-17 expression and attenuated Treg responses. Using a model of experimental colitis, we observed that mice lacking NFAT5 in T cells exhibited exacerbated intestinal colitis and enhanced expression of IFNγ in draining lymph nodes and colon. These results show that NFAT5 can modulate different T-cell responses depending on stress conditions and stimulatory context.
• dc.description.sponsorship JA was funded by the Spanish Ministry of Economy and Competitiveness (SAF2011-24268, cofunded by the European Regional Development Fund), and Fundació la Marató TV3 (122530). CL-R was funded by the Spanish Ministry of Economy and Competitiveness (SAF2012-36535, SAF2015-71363-R, cofunded by the European Regional Development Fund). CL-R is a recipient of an ICREA Acadèmia award from Institució Catalana de Recerca i Estudis Avançats (ICREA, Generalitat de Catalunya). JA and CL-R also acknowledge funding support from Generalitat de Catalunya (2009SGR601, 2014SGR1153) and the Spanish Ministry of Economy and Competitiveness, through the 'María de Maeztu' Program for Units of Excellence in R&D (MDM-2014-0370). RM was funded by the Spanish Ministry of Economy and Competitiveness (SAF2011-22463 and SAF2014-55088-R, cofunded by the European Regional Development Fund). MA was supported by predoctoral fellowships from Generalitat de Catalunya (FI-DGR program 2009) and the Spanish Ministry of Education, Culture and Sports (FPU program, AP2010-5411). MI was partially supported by a grant from the Spanish Ministry of Economy and Competitiveness (IPT2011-1527-010000). ST is the recipient of a predoctoral fellowship of the Spanish Ministry of Economy and Competitiveness (BES-2013-062670).
• dc.format.mimetype application/pdfca
• dc.identifier.citation Alberdi Ibarzabal M, Iglesias M, Tejedor Vaquero S, Merino R, López Rodríguez MC, Aramburu J. Context-dependent regulation of Th17-associated genes and IFNγ expression by the transcription factor NFAT5. Immunology and Cell Biology. 2017;95:56-67. DOI: 10.1038/icb.2016.69
• dc.identifier.doi http://dx.doi.org/10.1038/icb.2016.69
• dc.identifier.issn 0818-9641
• dc.identifier.uri http://hdl.handle.net/10230/28263
• dc.language.iso eng
• dc.publisher Nature Publishing Groupca
• dc.relation.ispartof Immunology and Cell Biology. 2017;95:56-67
• dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SAF2011-24268
• dc.rights © Nature Publishing Group. This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
• dc.subject.other Genètica
• dc.subject.other Cèl·lules T
• dc.subject.other Estrès
• dc.title Context-dependent regulation of Th17-associated genes and IFNγ expression by the transcription factor NFAT5ca
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion