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Title

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

AuthorsBuxadé, María; Huerga Encabo, Hector; Riera-Borrull, Marta; Quintana-Gallardo, Lucía; López-Cotarelo, Pilar; Tellechea, Mónica; Martínez-Martínez, Sara; Redondo, Juan Miguel ; Martín Caballero, Juan; Flores, Juana María; Bosch, Elena ; Rodríguez-Fernández, José Luis ; Aramburu, Jose; López-Rodríguez, Cristina
KeywordsTranscription factor NFAT5
Adipose-tissue macrophages
Bare lymphocyte syndrome
Class-II transactivator
CD4(+) T-cells
NF-Kappa-B
Major histocompatibility
Gene-expression
Allograft-rejection
IFN-Gamma
Issue Date16-Oct-2018
PublisherRockefeller University Press
CitationJ Exp Med 215:11(2901–2918) (2018)
AbstractMHCII 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.
Description25 p.-5 fig.-5 fig. supl.-2 tab. supl.
Publisher version (URL)https://doi.org/10.1084/jem.20180314
URIhttp://hdl.handle.net/10261/173700
DOI10.1084/jem.20180314
ISSN0022-1007
E-ISSN1540-9538
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