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
| Autor: | Hartmut Kleinert, Angelika B. Reske-Kunz, Svetlana Usanova, Ean-Jeong Seo, Matthias Bros, Jonathan Schupp, Evelyn Montermann, Diana Buchmüller, Thomas Efferth, Franziska Bollmann, Mahmoud Youns, Verena Kollek |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
T cell Population interleukin-10 dexamethasone Biology CFLAR 03 medical and health sciences 0302 clinical medicine Immune system mir-223 microRNA medicine Pharmacology (medical) education Antigen-presenting cell Original Research miRNA Regulation of gene expression Pharmacology education.field_of_study lcsh:RM1-950 mmu-miR-223-3p tolerogenic dendritic cells Cell biology 030104 developmental biology medicine.anatomical_structure lcsh:Therapeutics. Pharmacology 030215 immunology |
| Zdroj: | Frontiers in Pharmacology, Vol 9 (2018) Frontiers in Pharmacology |
| ISSN: | 1663-9812 |
| DOI: | 10.3389/fphar.2018.00915 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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