Mostra el registre parcial de l'element
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.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.issn | 0022-1007 |
dc.identifier.uri | http://hdl.handle.net/10230/37190 |
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.language.iso | eng |
dc.publisher | Rockefeller University Press |
dc.relation.ispartof | J Exp Med. 2018; 215(11):2901-2918 |
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.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.identifier.doi | http://dx.doi.org/10.1084/jem.20180314 |
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.accessRights | info:eu-repo/semantics/openAccess |
dc.type.version | info:eu-repo/semantics/publishedVersion |