Gene expression induced by Toll-like receptors in macrophages requires the transcription factor NFAT5

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  • dc.contributor.author Buxadé Fortuny, Mariaca
  • dc.contributor.author Lunazzi, Giuliaca
  • dc.contributor.author Minguillón Pedreño, Jordica
  • dc.contributor.author Iborra Mallol, Salvador, 1978-2011ca
  • dc.contributor.author Berga-Bolaños, Rosaca
  • dc.contributor.author Del Val, Margaritaca
  • dc.contributor.author Aramburu, José (Aramburu Beltrán)ca
  • dc.contributor.author López Rodríguez, M. Cristinaca
  • dc.date.accessioned 2015-06-15T07:18:53Z
  • dc.date.available 2015-06-15T07:18:53Z
  • dc.date.issued 2012ca
  • dc.description.abstract Toll-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.en
  • dc.description.sponsorship C. López-Rodríguez was supported by the Ramón y Cajal and I3 Researchers Programmes and grants from the Spanish Government (SAF2006-04913 and SAF2009-08066) and European Union (MCIRG516308). J. Aramburu was supported by grants from the Spanish Government (BFU2008-01070 and SAF2011-24268), and Distinció de la Generalitat de Catalunya per a la Promoció de la Recerca Universitària. Research in the laboratories of C. López-Rodríguez and J. Aramburu is also supported by Fundació la Marató TV3 (030230/31, 080730), Spanish Ministry of Health (ISCIII-RETIC RD06/0009-FEDER), and Generalitat de Catalunya (2009 SGR 601). M. Buxadé was supported by a Beatriu de Pinós postdoctoral contract from Generalitat de Catalunya. S. Iborra was supported by a Sara Borrell postdoctoral contract from the Ministry of Health of Spain. J. Minguillón and R. Berga-Bolaños were supported by predoctoral fellowships from the Spanish Government.en
  • dc.format.mimetype application/pdfca
  • dc.identifier.citation Buxadé 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.20111569ca
  • dc.identifier.doi http://dx.doi.org/10.1084/jem.20111569
  • dc.identifier.issn 0022-1007ca
  • dc.identifier.uri http://hdl.handle.net/10230/23816
  • dc.language.iso engca
  • dc.publisher Rockefeller University Pressca
  • dc.relation.ispartof Journal of experimental medicine. 2012;209(2):379-393
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PN/SAF2006-04913
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SAF2009-08066
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BFU2008-01070
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SAF2011-24268
  • dc.rights This 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/).en
  • dc.rights.accessRights info:eu-repo/semantics/openAccessca
  • dc.rights.uri http://creativecommons.org/licenses/by-nc-sa/3.0/
  • dc.subject.other Regulació genèticaca
  • dc.subject.other Metabolismeca
  • dc.subject.other Cèl·lules T -- Receptorsca
  • dc.subject.other Factors de transcripcióca
  • dc.title Gene expression induced by Toll-like receptors in macrophages requires the transcription factor NFAT5en
  • dc.type info:eu-repo/semantics/articleca
  • dc.type.version info:eu-repo/semantics/publishedVersionca

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