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Author | dc.contributor.author | García González, Paulina | |
Author | dc.contributor.author | Maggi, Jaxaira | |
Author | dc.contributor.author | Schinnerling, Katina | |
Author | dc.contributor.author | Sepúlveda Gutiérrez, Alejandro | |
Author | dc.contributor.author | Soto, Lilian | |
Author | dc.contributor.author | Neira, Oscar | |
Author | dc.contributor.author | Mehdi, Ahmed M. | |
Author | dc.contributor.author | Nel, Hendrik J. | |
Author | dc.contributor.author | Pesce, Bárbara | |
Author | dc.contributor.author | Aravena, Octavio | |
Author | dc.contributor.author | Molina, María Carmen | |
Author | dc.contributor.author | Catalán, Diego | |
Author | dc.contributor.author | Thomas, Ranjeny | |
Author | dc.contributor.author | Verdugo Salgado, Ricardo | |
Admission date | dc.date.accessioned | 2019-10-30T15:23:54Z | |
Available date | dc.date.available | 2019-10-30T15:23:54Z | |
Publication date | dc.date.issued | 2019 | |
Cita de ítem | dc.identifier.citation | Frontiers in Immunology, Volumen 10, Issue MAY, 2019, | |
Identifier | dc.identifier.issn | 16643224 | |
Identifier | dc.identifier.other | 10.3389/fimmu.2019.01171 | |
Identifier | dc.identifier.uri | https://repositorio.uchile.cl/handle/2250/172347 | |
Abstract | dc.description.abstract | Copyright © 2019 García-González, Maggi, Schinnerling, Sepúlveda-Gutiérrez, Soto, Neira, Mehdi, Nel, Pesce, Aravena, Molina, Catalán, Thomas, Verdugo and Aguillón.The potential of tolerogenic dendritic cells (tolDCs) to shape immune responses and restore tolerance has turn them into a promising therapeutic tool for cellular therapies directed toward immune regulation in autoimmunity. Although the cellular mechanisms by which these cells can exert their regulatory function are well-known, the mechanisms driving their differentiation and function are still poorly known, and the variety of stimuli and protocols applied to differentiate DCs toward a tolerogenic phenotype makes it even more complex to underpin the molecular features involved in their function. Through transcriptional profiling analysis of monocyte-derived tolDCs modulated with dexamethasone (Dex) and activated with monophosphoryl lipid A (MPLA), known as DM-DCs, we were able to identify MYC as one of the transcriptional regulators of several genes differentially expressed on DM-DCs compared to MPLA-matured DCs (M-DCs) and untreated/immature DCs (DCs) as revealed by Ingenuity Pathway Analysis (IPA) upstream regulators evaluation. Additionally, MYC was also amidst the most upregulated genes in DM-DCs, finding that was confirmed at a transcriptional as well as at a protein level. Blockade of transactivation of MYC target genes led to the downregulation of tolerance-related markers IDO1 and JAG1. MYC blockade also led to downregulation of PLZF and STAT3, transcription factors associated with immune regulation and inhibition of DC maturation, further supporting a role of MYC as an upstream regulator contributing to the regulatory phenotype of DM-DCs. On the other hand, we had previously shown that fatty acid oxidation, oxidative metabolism and zinc homeostasis are amongst the main biological functions represented in DM-DCs, and here we show that DM-DCs exhibit higher intracellular expression of ROS and Zinc compared to mature M-DCs and DCs. Taken together, these findings suggest that the regulatory profile of DM-DCs is partly shaped by the effect of the transcriptional regulation of tolerance-inducing genes by MYC and the modulation of oxidative metabolic processes and signaling mediators such as Zinc and ROS. | |
Lenguage | dc.language.iso | en | |
Publisher | dc.publisher | Frontiers Media S.A. | |
Type of license | dc.rights | Attribution-NonCommercial-NoDerivs 3.0 Chile | |
Link to License | dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/cl/ | |
Source | dc.source | Frontiers in Immunology | |
Keywords | dc.subject | DC transcription factors | |
Keywords | dc.subject | Dexamethasone-modulated and MPLA-activated DC | |
Keywords | dc.subject | ROS metabollism in DC | |
Keywords | dc.subject | Tolerance mechanism | |
Keywords | dc.subject | Tolerogenic dendritic cells (tDC) | |
Keywords | dc.subject | Zinc metabollism in DC | |
Título | dc.title | Regulation of tolerogenic features on dexamethasone-modulated MPLA-activated dendritic cells by Myc | |
Document type | dc.type | Artículo de revista | |
dcterms.accessRights | dcterms.accessRights | Acceso Abierto | |
Cataloguer | uchile.catalogador | SCOPUS | |
Indexation | uchile.index | Artículo de publicación SCOPUS | |
uchile.cosecha | uchile.cosecha | SI | |
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