| First Author | Alberdi M | Year | 2017 |
| Journal | Immunol Cell Biol | Volume | 95 |
| Issue | 1 | Pages | 56-67 |
| PubMed ID | 27479742 | Mgi Jnum | J:358497 |
| Mgi Id | MGI:6844245 | Doi | 10.1038/icb.2016.69 |
| Citation | Alberdi M, et al. (2017) Context-dependent regulation of Th17-associated genes and IFNgamma expression by the transcription factor NFAT5. Immunol Cell Biol 95(1):56-67 |
| abstractText | Stress-activated transcription factors influence T-cell function in different physiopathologic contexts. NFAT5, a relative of nuclear factor kappaB 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 RORgammat 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 gamma (IFNgamma) 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 IFNgamma in draining lymph nodes and colon. These results show that NFAT5 can modulate different T-cell responses depending on stress conditions and stimulatory context. |
