Macrophage-specific MHCII expression is regulated by a remote Ciita enhancer controlled by NFAT5

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  • dc.contributor.author Buxadé Fortuny, Maria
  • dc.contributor.author Huerga Encabo, Hector, 1989-
  • dc.contributor.author Riera-Borrull, Marta
  • dc.contributor.author Quintana-Gallardo, Lucía
  • dc.contributor.author López-Cotarelo, Pilar
  • dc.contributor.author Tellechea Recarte, Mónica, 1989-
  • dc.contributor.author Martínez-Martínez, Sara
  • dc.contributor.author Redondo, Juan Miguel
  • dc.contributor.author Martín Caballero, Juan
  • dc.contributor.author Flores, Juana M.
  • dc.contributor.author Bosch Fusté, Elena
  • dc.contributor.author Rodríguez-Fernández, José Luis
  • dc.contributor.author Aramburu, José (Aramburu Beltrán)
  • dc.contributor.author López Rodríguez, M. Cristina
  • dc.date.accessioned 2019-05-08T07:32:33Z
  • dc.date.available 2019-05-08T07:32:33Z
  • dc.date.issued 2018
  • dc.description.abstract MHCII in antigen-presenting cells (APCs) is a key regulator of adaptive immune responses. Expression of MHCII genes is controlled by the transcription coactivator CIITA, itself regulated through cell type-specific promoters. Here we show that the transcription factor NFAT5 is needed for expression of Ciita and MHCII in macrophages, but not in dendritic cells and other APCs. NFAT5-deficient macrophages showed defective activation of MHCII-dependent responses in CD4+ T lymphocytes and attenuated capacity to elicit graft rejection in vivo. Ultrasequencing analysis of NFAT5-immunoprecipitated chromatin uncovered an NFAT5-regulated region distally upstream of Ciita This region was required for CIITA and hence MHCII expression, exhibited NFAT5-dependent characteristics of active enhancers such as H3K27 acetylation marks, and required NFAT5 to interact with Ciita myeloid promoter I. Our results uncover an NFAT5-regulated mechanism that maintains CIITA and MHCII expression in macrophages and thus modulates their T lymphocyte priming capacity.
  • dc.description.sponsorship This work was supported by the Spanish Ministry of Economy and Competitiveness (MINECO), Agencia Estatal de Investigación, and European Regional Development Fund (SAF2012-36535, SAF2015-71363-R, and BFU2016-77961-P), and Fundació la Marató de TV3 (1225-30 and 201619-30). We also acknowledge funding support from Generalitat de Catalunya (2014SGR1153, 2017SGR888, and 2017SGR702) and MINECO through the “Unidad de Excelencia María de Maeztu” funded by MINECO (MDM-2014-0370). H. Huerga Encabo was supported by a predoctoral fellowship of the Spanish Ministerio de Educación, Cultura y Deporte (FPU13/01798). M. Tellechea was supported by fellowships from Fundació Catalunya-La Pedrera (2011) and Generalitat de Catalunya (FI-DGR program 2013). C. López-Rodríguez is a recipient of an ICREA Acadèmia award from Institució Catalana de Recerca i Estudis Avançats (ICREA, Generalitat de Catalunya).
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Buxadé M, Huerga Encabo H, Riera-Borrull M, Quintana-Gallardo L, López-Cotarelo P, Tellechea M, Martínez-Martínez S, Redondo JM, Martín-Caballero J, Flores JM, Bosch E, Rodríguez-Fernández JL, Aramburu J, López-Rodríguez C. Macrophage-specific MHCII expression is regulated by a remote Ciita enhancer controlled by NFAT5. J Exp Med. 2018; 215(11):2901-2918. DOI 10.1084/jem.20180314
  • dc.identifier.doi http://dx.doi.org/10.1084/jem.20180314
  • dc.identifier.issn 0022-1007
  • dc.identifier.uri http://hdl.handle.net/10230/37190
  • dc.language.iso eng
  • dc.publisher Rockefeller University Press
  • dc.relation.ispartof J Exp Med. 2018; 215(11):2901-2918
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2012-36535
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2015-71363-R
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2016-77961-P
  • dc.rights © 2018 Buxadé et al. 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 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri https://creativecommons.org/licenses/by-nc-sa/4.0/
  • dc.title Macrophage-specific MHCII expression is regulated by a remote Ciita enhancer controlled by NFAT5
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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