Alberdi Ibarzabal, Maria, 1986-Iglesias, MarcosTejedor Vaquero, Sonia, 1988-Merino, RamónLópez Rodríguez, M. CristinaAramburu, José (Aramburu Beltrán)2017-03-202017-03-202017Alberdi 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.2016.690818-9641http://hdl.handle.net/10230/28263Stress-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.application/pdfeng© 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/.GenèticaCèl·lules TEstrèsinfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1038/icb.2016.69info:eu-repo/semantics/openAccess