Differentially Tolerized Mouse Antigen Presenting Cells Share a Common miRNA Signature Including Enhanced mmu-miR-223-3p Expression Which Is Sufficient to Imprint a Protolerogenic State

Publication type:
Journal article
Metadata:
Autoren
  • Matthias Bros
  • Mahmoud Youns
  • Verena Kollek
  • Diana Buchmueller
  • Franziska Bollmann
  • Ean-Jeong Seo
  • Jonathan Schupp
  • Evelyn Montermann
  • Svetlana Usanova
  • Hartmut Kleinert
  • Thomas Efferth
  • Angelika B Reske-Kunz
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000441911000001&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.3389/fphar.2018.00915
eISSN
1663-9812
Externe Identifier
  • Clarivate Analytics Document Solution ID: GQ7II
  • PubMed Identifier: 30174602
Zeitschrift
FRONTIERS IN PHARMACOLOGY
Schlüsselwörter
  • dexamethasone
  • interleukin-10
  • miRNA
  • mmu-miR-223-3p
  • tolerogenic dendritic cells
Artikelnummer
ARTN 915
Datum der Veröffentlichung
2018
Status
Published
Titel
Differentially Tolerized Mouse Antigen Presenting Cells Share a Common miRNA Signature Including Enhanced mmu-miR-223-3p Expression Which Is Sufficient to Imprint a Protolerogenic State
Sub types
  • Article
Ausgabe der Zeitschrift
9

Data source: Web of Science (Lite)

Other metadata sources:
Autoren
  • Matthias Bros
  • Mahmoud Youns
  • Verena Kollek
  • Diana Buchmüller
  • Franziska Bollmann
  • Ean-Jeong Seo
  • Jonathan Schupp
  • Evelyn Montermann
  • Svetlana Usanova
  • Hartmut Kleinert
  • Thomas Efferth
  • Angelika B Reske-Kunz
DOI
10.3389/fphar.2018.00915
eISSN
1663-9812
Zeitschrift
Frontiers in Pharmacology
Online publication date
2018
Status
Published online
Herausgeber
Frontiers Media SA
Herausgeber URL
http://dx.doi.org/10.3389/fphar.2018.00915
Datum der Datenerfassung
2019
Titel
Differentially Tolerized Mouse Antigen Presenting Cells Share a Common miRNA Signature Including Enhanced mmu-miR-223-3p Expression Which Is Sufficient to Imprint a Protolerogenic State
Ausgabe der Zeitschrift
9

Data source: Crossref

Abstract
Dendritic cells (DCs) are pivotal for the induction and maintenance of antigen-specific tolerance and immunity. miRNAs mediate post-transcriptional gene regulation and control in part the differentiation and stimulation-induced immunogenic function of DCs. However, the relevance of miRNAs for the induction and maintenance of a tolerogenic state of DCs has scarcely been highlighted yet. We differentiated mouse bone marrow cells to conventional/myeloid DCs or to tolerogenic antigen presenting cells (APCs) by using a glucocorticoid (dexamethasone) or interleukin-10, and assessed the miRNA expression patterns of unstimulated and LPS-stimulated cell populations by array analysis and QPCR. Differentially tolerized mouse APCs convergingly down-regulated a set of miRNA species at either state of activation as compared with the corresponding control DC population (mmu-miR-9-5p, mmu-miR-9-3p, mmu-miR-155-5p). These miRNAs were also upregulated in control DCs in response to stimulation. In contrast, miRNAs that were convergingly upregulated in both tolerized APC groups at stimulated state (mmu-miR-223-3p, mmu-miR-1224-5p) were downregulated in control DCs in response to stimulation. Overexpression of mmu-miR-223-3p in DCs was sufficient to prevent stimulation-associated acquisition of potent T cell stimulatory capacity. Overexpression of mmu-miR-223-3p in a DC line resulted in attenuated expression of known (Cflar, Rasa1, Ras) mRNA targets of this miRNA species shown to affect pathways that control DC activation. Taken together, we identified sets of miRNAs convergingly regulated in differentially tolerized APCs, which may contribute to imprint stimulation-resistant tolerogenic function as demonstrated for mmu-miR-223-3p. Knowledge of miRNAs with protolerogenic function enables immunotherapeutic approaches aimed to modulate immune responses by regulating miRNA expression.
Addresses
  • Department of Dermatology, University Medical Center, Johannes Gutenberg University, Mainz, Germany.
Autoren
  • Matthias Bros
  • Mahmoud Youns
  • Verena Kollek
  • Diana Buchmüller
  • Franziska Bollmann
  • Ean-Jeong Seo
  • Jonathan Schupp
  • Evelyn Montermann
  • Svetlana Usanova
  • Hartmut Kleinert
  • Thomas Efferth
  • Angelika B Reske-Kunz
DOI
10.3389/fphar.2018.00915
eISSN
1663-9812
Externe Identifier
  • PubMed Identifier: 30174602
  • PubMed Central ID: PMC6108336
Funding acknowledgements
  • Deutsche Forschungsgemeinschaft: SFB 1066
Open access
true
ISSN
1663-9812
Zeitschrift
Frontiers in pharmacology
Sprache
eng
Medium
Electronic-eCollection
Online publication date
2018
Open access status
Open Access
Paginierung
915
Datum der Veröffentlichung
2018
Status
Published
Publisher licence
CC BY
Datum der Datenerfassung
2018
Titel
Differentially Tolerized Mouse Antigen Presenting Cells Share a Common miRNA Signature Including Enhanced mmu-miR-223-3p Expression Which Is Sufficient to Imprint a Protolerogenic State.
Sub types
  • research-article
  • Journal Article
Ausgabe der Zeitschrift
9

Files

https://www.frontiersin.org/articles/10.3389/fphar.2018.00915/pdf https://europepmc.org/articles/PMC6108336?pdf=render

Data source: Europe PubMed Central

Abstract
Dendritic cells (DCs) are pivotal for the induction and maintenance of antigen-specific tolerance and immunity. miRNAs mediate post-transcriptional gene regulation and control in part the differentiation and stimulation-induced immunogenic function of DCs. However, the relevance of miRNAs for the induction and maintenance of a tolerogenic state of DCs has scarcely been highlighted yet. We differentiated mouse bone marrow cells to conventional/myeloid DCs or to tolerogenic antigen presenting cells (APCs) by using a glucocorticoid (dexamethasone) or interleukin-10, and assessed the miRNA expression patterns of unstimulated and LPS-stimulated cell populations by array analysis and QPCR. Differentially tolerized mouse APCs convergingly down-regulated a set of miRNA species at either state of activation as compared with the corresponding control DC population (mmu-miR-9-5p, mmu-miR-9-3p, mmu-miR-155-5p). These miRNAs were also upregulated in control DCs in response to stimulation. In contrast, miRNAs that were convergingly upregulated in both tolerized APC groups at stimulated state (mmu-miR-223-3p, mmu-miR-1224-5p) were downregulated in control DCs in response to stimulation. Overexpression of mmu-miR-223-3p in DCs was sufficient to prevent stimulation-associated acquisition of potent T cell stimulatory capacity. Overexpression of mmu-miR-223-3p in a DC line resulted in attenuated expression of known (Cflar, Rasa1, Ras) mRNA targets of this miRNA species shown to affect pathways that control DC activation. Taken together, we identified sets of miRNAs convergingly regulated in differentially tolerized APCs, which may contribute to imprint stimulation-resistant tolerogenic function as demonstrated for mmu-miR-223-3p. Knowledge of miRNAs with protolerogenic function enables immunotherapeutic approaches aimed to modulate immune responses by regulating miRNA expression.
Date of acceptance
2018
Autoren
  • Matthias Bros
  • Mahmoud Youns
  • Verena Kollek
  • Diana Buchmüller
  • Franziska Bollmann
  • Ean-Jeong Seo
  • Jonathan Schupp
  • Evelyn Montermann
  • Svetlana Usanova
  • Hartmut Kleinert
  • Thomas Efferth
  • Angelika B Reske-Kunz
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/30174602
DOI
10.3389/fphar.2018.00915
Externe Identifier
  • PubMed Central ID: PMC6108336
ISSN
1663-9812
Zeitschrift
Front Pharmacol
Schlüsselwörter
  • dexamethasone
  • interleukin-10
  • miRNA
  • mmu-miR-223-3p
  • tolerogenic dendritic cells
Sprache
eng
Country
Switzerland
Paginierung
915
Datum der Veröffentlichung
2018
Status
Published online
Titel
Differentially Tolerized Mouse Antigen Presenting Cells Share a Common miRNA Signature Including Enhanced mmu-miR-223-3p Expression Which Is Sufficient to Imprint a Protolerogenic State.
Sub types
  • Journal Article
Ausgabe der Zeitschrift
9

Data source: PubMed

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