Buxadé Fortuny, MariaLunazzi, GiuliaMinguillón Pedreño, JordiIborra Mallol, Salvador, 1978-2011Berga-Bolaños, RosaDel Val, MargaritaAramburu, José (Aramburu Beltrán)López Rodríguez, M. Cristina2015-06-152015-06-152012Buxadé M, Lunazzi G, Minguillón J, Iborra S, Berga-Bolaños R, del Val M et al. Gene expression induced by Toll-like receptors in macrophages requires the transcription factor NFAT5. J Exp Med. 2012;209(2):379-93. DOI: 10.1084/jem.201115690022-1007http://hdl.handle.net/10230/23816Toll-like receptors (TLRs) engage networks of transcriptional regulators to induce genes essential for antimicrobial immunity. We report that NFAT5, previously characterized as an osmostress responsive factor, regulates the expression of multiple TLR-induced genes in macrophages independently of osmotic stress. NFAT5 was essential for the induction of the key antimicrobial gene Nos2 (inducible nitric oxide synthase [iNOS]) in response to low and high doses of TLR agonists but is required for Tnf and Il6 mainly under mild stimulatory conditions, indicating that NFAT5 could regulate specific gene patterns depending on pathogen burden intensity. NFAT5 exhibited two modes of association with target genes, as it was constitutively bound to Tnf and other genes regardless of TLR stimulation, whereas its recruitment to Nos2 or Il6 required TLR activation. Further analysis revealed that TLR-induced recruitment of NFAT5 to Nos2 was dependent on inhibitor of κB kinase (IKK) β activity and de novo protein synthesis, and was sensitive to histone deacetylases. In vivo, NFAT5 was necessary for effective immunity against Leishmania major, a parasite whose clearance requires TLRs and iNOS expression in macrophages. These findings identify NFAT5 as a novel regulator of mammalian anti-pathogen responses.application/pdfengThis article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).Regulació genèticaMetabolismeCèl·lules T -- ReceptorsFactors de transcripcióinfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1084/jem.20111569info:eu-repo/semantics/openAccess