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

Buxadé Fortuny, MariaHuerga Encabo, Hector, 1989-Riera-Borrull, MartaQuintana-Gallardo, LucíaLópez-Cotarelo, PilarTellechea Recarte, Mónica, 1989-Martínez-Martínez, SaraRedondo, Juan MiguelMartín Caballero, JuanFlores, Juana M.Bosch Fusté, ElenaRodríguez-Fernández, José LuisAramburu, José (Aramburu Beltrán)López Rodríguez, M. Cristina2019-05-082019-05-082018Buxadé 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.201803140022-1007http://hdl.handle.net/10230/37190MHCII 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.application/pdfeng© 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/).Macrophage-specific MHCII expression is regulated by a remote Ciita enhancer controlled by NFAT5info:eu-repo/semantics/articlehttp://dx.doi.org/10.1084/jem.20180314info:eu-repo/semantics/openAccess