{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T17:35:09Z","timestamp":1790616909210,"version":"4.1.0"},"reference-count":66,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2010,12,1]],"date-time":"2010-12-01T00:00:00Z","timestamp":1291161600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Immune cells rely on the transcription factor NFAT5 to adapt to hypertonic stress. The hypertonicity-dependent role of NFAT5 in T cells in vivo remains unclear because mouse models of NFAT5 deficiency have produced substantially different T cell phenotypes. In this study, we analyzed the T cell compartment in NFAT5-null and T cell-specific NFAT5 knockout mice. We found that NFAT5-null mice had constitutive, pronounced hypernatremia and suffered a severe immunodeficiency, with T cell lymphopenia, altered CD8 naive\/memory homeostasis, and inability to reject allogeneic tumors. By contrast, T cell-specific NFAT5 knockout mice had normal plasma tonicity, rejected allogeneic tumors, and exhibited only a mild, low-penetrance memory bias in CD8 cells. Notably, when T cells from these mice were cultured ex vivo in hypernatremic media, they exhibited features found in NFAT5-null mice, with pronounced naive\/memory imbalance and impaired homeostatic survival in response to IL-7, as well as a severe inhibition of their mitogen-induced proliferation. By analyzing surface receptors whose expression might be affected in NFAT5-deficient cells, we identified CD24 as a novel NFAT5 target induced by hypertonicity both in vitro and in vivo, and required to sustain T cell expansion under osmostress. NFAT5 bound to the Cd24 promoter in response to hypertonicity facilitated the local derepression of chromatin and enhanced the expression of CD24 mRNA and protein. Altogether, our results indicate that the systemic hypernatremia of NFAT5-null mice is a major contributor to their immunodeficiency, and highlight the role of NFAT5 and CD24 in the homeostasis of T cells under osmostress in vivo.<\/jats:p>","DOI":"10.4049\/jimmunol.1001232","type":"journal-article","created":{"date-parts":[[2010,10,30]],"date-time":"2010-10-30T03:06:24Z","timestamp":1288407984000},"page":"6624-6635","source":"Crossref","is-referenced-by-count":48,"title":["NFAT5 Regulates T Lymphocyte Homeostasis and CD24-Dependent T Cell Expansion under Pathologic Hypernatremia"],"prefix":"10.1093","volume":"185","author":[{"given":"Rosa","family":"Berga-Bola\u00f1os","sequence":"first","affiliation":[{"name":"Immunology Unit, Department of Experimental and Health Sciences, Pompeu Fabra University, Barcelona Biomedical Research Park , Barcelona 08003 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Drews-Elger","sequence":"additional","affiliation":[{"name":"Immunology Unit, Department of Experimental and Health Sciences, Pompeu Fabra University, Barcelona Biomedical Research Park , Barcelona 08003 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose","family":"Aramburu","sequence":"additional","affiliation":[{"name":"Immunology Unit, Department of Experimental and Health Sciences, Pompeu Fabra University, Barcelona Biomedical Research Park , Barcelona 08003 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"L\u00f3pez-Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Immunology Unit, Department of Experimental and Health Sciences, Pompeu Fabra University, Barcelona Biomedical Research Park , Barcelona 08003 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2010,12,1]]},"reference":[{"key":"2025032412144115200_r1","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1038\/nri853","article-title":"Maintaining the norm: T-cell homeostasis","volume":"2","author":"Jameson","year":"2002","journal-title":"Nat. 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Immunol."},{"key":"2025032412144115200_r13","doi-asserted-by":"crossref","first-page":"7446","DOI":"10.4049\/jimmunol.174.11.7446","article-title":"The influence of age on T cell generation and TCR diversity","volume":"174","author":"Naylor","year":"2005","journal-title":"J. Immunol."},{"key":"2025032412144115200_r14","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1126\/science.272.5258.54","article-title":"Immunological memory and protective immunity: understanding their relation","volume":"272","author":"Ahmed","year":"1996","journal-title":"Science"},{"key":"2025032412144115200_r15","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/S0167-5699(00)01714-X","article-title":"Ageing of lymphocytes and lymphocytes in the aged","volume":"21","author":"Globerson","year":"2000","journal-title":"Immunol. 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Chem."},{"key":"2025032412144115200_r35","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1172\/JCI9154","article-title":"Generation and phenotype of mice harboring a nonsense mutation in the V2 vasopressin receptor gene","volume":"106","author":"Yun","year":"2000","journal-title":"J. Clin. Invest."},{"key":"2025032412144115200_r36","first-page":"317","article-title":"Hyperosmolar non-ketotic diabetic syndrome associated with rhabdomyolysis and acute renal failure: a case report and review of literature","volume":"16","author":"Ka","year":"2003","journal-title":"Diabetes Nutr. Metab."},{"key":"2025032412144115200_r37","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1007\/BF02849861","article-title":"Nonketotic hyperosmolar coma in a patient with type 1 diabetes-related diabetic nephropathy: case report","volume":"22","author":"Dogan","year":"2005","journal-title":"Adv. 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Biol."},{"key":"2025032412144115200_r42","doi-asserted-by":"crossref","first-page":"e5245","DOI":"10.1371\/journal.pone.0005245","article-title":"The transcription factor NFAT5 is required for cyclin expression and cell cycle progression in cells exposed to hypertonic stress","volume":"4","author":"Drews-Elger","year":"2009","journal-title":"PLoS ONE"},{"key":"2025032412144115200_r43","doi-asserted-by":"crossref","first-page":"ra5","DOI":"10.1126\/scisignal.2000081","article-title":"Brx mediates the response of lymphocytes to osmotic stress through the activation of NFAT5","volume":"2","author":"Kino","year":"2009","journal-title":"Sci. Signal."},{"key":"2025032412144115200_r44","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1038\/nm.1960","article-title":"Macrophages regulate salt-dependent volume and blood pressure by a vascular endothelial growth factor-C-dependent buffering mechanism","volume":"15","author":"Machnik","year":"2009","journal-title":"Nat. Med."},{"key":"2025032412144115200_r45","doi-asserted-by":"crossref","first-page":"10673","DOI":"10.1073\/pnas.0403139101","article-title":"NFAT5\/TonEBP mutant mice define osmotic stress as a critical feature of the lymphoid microenvironment","volume":"101","author":"Go","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025032412144115200_r46","doi-asserted-by":"crossref","first-page":"9398","DOI":"10.1073\/pnas.152665399","article-title":"Defective T cell development and function in calcineurin A beta -deficient mice","volume":"99","author":"Bueno","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025032412144115200_r47","doi-asserted-by":"crossref","first-page":"7214","DOI":"10.1073\/pnas.96.13.7214","article-title":"NFAT5, a constitutively nuclear NFAT protein that does not cooperate with Fos and Jun","volume":"96","author":"Lopez-Rodr\u00edguez","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025032412144115200_r48","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1084\/jem.175.2.437","article-title":"Heat-stable antigen is a costimulatory molecule for CD4 T cell growth","volume":"175","author":"Liu","year":"1992","journal-title":"J. Exp. Med."},{"key":"2025032412144115200_r49","first-page":"245","volume-title":"Antibodies: a laboratory manual.","author":"Harlow","year":"1988"},{"key":"2025032412144115200_r50","first-page":"343","article-title":"Autocrine regulation of T-lymphocyte proliferation: differential induction of IL-2 and IL-2 receptor","volume":"65","author":"Cantrell","year":"1988","journal-title":"Immunology"},{"key":"2025032412144115200_r51","doi-asserted-by":"crossref","first-page":"23345","DOI":"10.1016\/S0021-9258(19)49469-6","article-title":"The heat stable antigen (mouse CD24) gene is differentially regulated but has a housekeeping promoter","volume":"268","author":"Wenger","year":"1993","journal-title":"J. Biol. Chem."},{"key":"2025032412144115200_r52","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/j.cell.2007.02.005","article-title":"Chromatin modifications and their function","volume":"128","author":"Kouzarides","year":"2007","journal-title":"Cell"},{"key":"2025032412144115200_r53","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/S1074-7613(01)00170-4","article-title":"How much TCR does a T cell need?","volume":"15","author":"Labrecque","year":"2001","journal-title":"Immunity"},{"key":"2025032412144115200_r54","doi-asserted-by":"crossref","first-page":"8744","DOI":"10.1073\/pnas.141218898","article-title":"How alpha beta T cells deal with induced TCR alpha ablation","volume":"98","author":"Polic","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025032412144115200_r55","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.exger.2005.12.002","article-title":"Telomeres, immune aging and autoimmunity","volume":"41","author":"Goronzy","year":"2006","journal-title":"Exp. Gerontol."},{"key":"2025032412144115200_r56","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/j.it.2006.05.002","article-title":"Immunity and age: living in the past?","volume":"27","author":"Woodland","year":"2006","journal-title":"Trends Immunol."},{"key":"2025032412144115200_r57","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/nri2471","article-title":"The ageing immune system: is it ever too old to become young again?","volume":"9","author":"Dorshkind","year":"2009","journal-title":"Nat. Rev. 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Immunol."},{"key":"2025032412144115200_r62","doi-asserted-by":"crossref","first-page":"3521","DOI":"10.1038\/sj.emboj.7601796","article-title":"Transmembrane mucins Hkr1 and Msb2 are putative osmosensors in the SHO1 branch of yeast HOG pathway","volume":"26","author":"Tatebayashi","year":"2007","journal-title":"EMBO J."},{"key":"2025032412144115200_r63","doi-asserted-by":"crossref","first-page":"1722","DOI":"10.1126\/science.1168988","article-title":"CD24 and Siglec-10 selectively repress tissue damage-induced immune responses","volume":"323","author":"Chen","year":"2009","journal-title":"Science"},{"key":"2025032412144115200_r64","doi-asserted-by":"crossref","first-page":"2780","DOI":"10.1073\/pnas.92.7.2780","article-title":"Demonstration that polyol accumulation is responsible for diabetic cataract by the use of transgenic mice expressing the aldose reductase gene in the lens","volume":"92","author":"Lee","year":"1995","journal-title":"Proc. Natl. Acad. Sci. 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