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dc.contributor.author
Morante Palacios, Octavio
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Ciudad, Laura
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Micheroli, Raphael
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De La Calle Fabregat, Carlos
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Li, Tianlu
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Barbisan, Gisela
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dc.contributor.author
Houtman, Miranda
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Edalat, Sam G.
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Frank Bertoncelj, Mojca
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Ospelt, Caroline
dc.contributor.author
Ballestar, Esteban
dc.date.available
2023-08-04T15:20:04Z
dc.date.issued
2022-01
dc.identifier.citation
Morante Palacios, Octavio; Ciudad, Laura; Micheroli, Raphael; De La Calle Fabregat, Carlos; Li, Tianlu; et al.; Coordinated glucocorticoid receptor and MAFB action induces tolerogenesis and epigenome remodeling in dendritic cells; Oxford University Press; Nucleic Acids Research; 50; 1; 1-2022; 108-126
dc.identifier.issn
1362-4962
dc.identifier.uri
http://hdl.handle.net/11336/206993
dc.description.abstract
Glucocorticoids (GCs) exert potent anti-inflammatory effects in immune cells through the glucocorticoid receptor (GR). Dendritic cells (DCs), central actors for coordinating immune responses, acquire tolerogenic properties in response to GCs. Tolerogenic DCs (tolDCs) have emerged as a potential treatment for various inflammatory diseases. To date, the underlying cell type-specific regulatory mechanisms orchestrating GC-mediated acquisition of immunosuppressive properties remain poorly understood. In this study, we investigated the transcriptomic and epigenomic remodeling associated with differentiation to DCs in the presence of GCs. Our analysis demonstrates a major role of MAFB in this process, in synergy with GR. GR and MAFB both interact with methylcytosine dioxygenase TET2 and bind to genomic loci that undergo specific demethylation in tolDCs. We also show that the role of MAFB is more extensive, binding to thousands of genomic loci in tolDCs. Finally, MAFB knockdown erases the tolerogenic properties of tolDCs and reverts the specific DNA demethylation and gene upregulation. The preeminent role of MAFB is also demonstrated in vivo for myeloid cells from synovium in rheumatoid arthritis following GC treatment. Our results imply that, once directly activated by GR, MAFB plays a critical role in orchestrating the epigenomic and transcriptomic remodeling that define the tolerogenic phenotype.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Oxford University Press
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dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
GLUCOCORTICOID RECEPTOR
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MAFB
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EPIGENOME
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DENDRITIC CELLS
dc.subject.classification
Bioquímica y Biología Molecular
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dc.subject.classification
Ciencias Biológicas
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CIENCIAS NATURALES Y EXACTAS
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dc.title
Coordinated glucocorticoid receptor and MAFB action induces tolerogenesis and epigenome remodeling in dendritic cells
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2023-07-07T18:00:20Z
dc.journal.volume
50
dc.journal.number
1
dc.journal.pagination
108-126
dc.journal.pais
Reino Unido
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dc.journal.ciudad
Oxford
dc.description.fil
Fil: Morante Palacios, Octavio. No especifíca;
dc.description.fil
Fil: Ciudad, Laura. No especifíca;
dc.description.fil
Fil: Micheroli, Raphael. Universitat Zurich; Suiza
dc.description.fil
Fil: De La Calle Fabregat, Carlos. No especifíca;
dc.description.fil
Fil: Li, Tianlu. No especifíca;
dc.description.fil
Fil: Barbisan, Gisela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET- La Plata. Instituto de Genética Veterinaria "Ing. Fernando Noel Dulout". Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Instituto de Genética Veterinaria; Argentina
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Fil: Houtman, Miranda. Universitat Zurich; Suiza
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Fil: Edalat, Sam G.. Universitat Zurich; Suiza
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Fil: Frank Bertoncelj, Mojca. Universitat Zurich; Suiza
dc.description.fil
Fil: Ospelt, Caroline. Universitat Zurich; Suiza
dc.description.fil
Fil: Ballestar, Esteban. No especifíca;
dc.journal.title
Nucleic Acids Research
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dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1093/nar/gkab1182
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