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The Cross-Talk between miR-511-3p and C-Type Lectin Receptors on Dendritic Cells Affects Dendritic Cell Function

Dennis Awuah, Meshal Alobaid, Arsalan Latif, Fabián Salazar, Richard D. Emes and Amir M. Ghaemmaghami
J Immunol May 22, 2019, ji1801108; DOI: https://doi.org/10.4049/jimmunol.1801108
Dennis Awuah
*Division of Immunology, School of Life Sciences, Faculty of Medicine and Health Sciences, University of Nottingham, Nottingham NG7 2RD, United Kingdom;
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Meshal Alobaid
*Division of Immunology, School of Life Sciences, Faculty of Medicine and Health Sciences, University of Nottingham, Nottingham NG7 2RD, United Kingdom;
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Arsalan Latif
*Division of Immunology, School of Life Sciences, Faculty of Medicine and Health Sciences, University of Nottingham, Nottingham NG7 2RD, United Kingdom;
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Fabián Salazar
*Division of Immunology, School of Life Sciences, Faculty of Medicine and Health Sciences, University of Nottingham, Nottingham NG7 2RD, United Kingdom;
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Richard D. Emes
†School of Veterinary Medicine and Science, University of Nottingham, Leicestershire LE12 5NT, United Kingdom; and
‡Advanced Data Analysis Centre, University of Nottingham, Leicestershire LE12 5NT, United Kingdom
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Amir M. Ghaemmaghami
*Division of Immunology, School of Life Sciences, Faculty of Medicine and Health Sciences, University of Nottingham, Nottingham NG7 2RD, United Kingdom;
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Key Points

  • The miR-511-3p regulates MR and DC-SIGN expression in human DCs.

  • Silencing miR-511-3p expression promotes anti-inflammatory DC phenotype.

  • Changes in miR-511-3p levels in DCs affect T cell polarization in DC–T coculture.

Abstract

MicroRNAs are small, noncoding RNAs that function as posttranscriptional modulators of gene expression by binding target mRNAs and inhibiting translation. They are therefore crucial regulators of several biological as well as immunological events. Recently, miR-511-3p has been implicated in the development and differentiation of APCs, such as dendritic cells (DCs), and regulating several human diseases. Interestingly, miR-511-3p is embedded within the human MRC1 gene that encodes the mannose receptor. In this study, we sought to examine the impact of miR-511-3p up- or downregulation on human DC surface phenotype, cytokine profile, immunogenicity (using IDO activity as a surrogate), and downstream T cell polarization. Using gene silencing and a selection of microRNA mimics, we could successfully suppress or induce the expression of miR-511-3p in DCs. Consequently, we show for the first time, to our knowledge, that inhibition and/or overexpression of miR-511-3p has opposing effects on the expression levels of two key C-type lectin receptors, namely the mannose receptor and DC-specific ICAM 3 nonintegrin at protein and mRNA levels, thereby affecting C-type lectin receptor–induced modulation of IDO activity in DCs. Furthermore, we show that downregulation of miR-511-3p drives an anti-inflammatory DC response characterized by IL-10 production. Interestingly, the miR-511-3plow DCs also promoted IL-4 secretion and suppressed IL-17 in cocultures with autologous T cells. Together, our data highlight the potential role of miR-511 in regulating DC function and downstream events leading to Th polarization and immune modulation.

Footnotes

  • This work was supported in part by the University of Nottingham Vice-Chancellor's Scholarship for Research Excellence (International) (to D.A.).

  • The online version of this article contains supplemental material.

  • Received August 10, 2018.
  • Accepted April 29, 2019.
  • Copyright © 2019 by The American Association of Immunologists, Inc.
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The Journal of Immunology: 209 (4)
The Journal of Immunology
Vol. 209, Issue 4
15 Aug 2022
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The Cross-Talk between miR-511-3p and C-Type Lectin Receptors on Dendritic Cells Affects Dendritic Cell Function
Dennis Awuah, Meshal Alobaid, Arsalan Latif, Fabián Salazar, Richard D. Emes, Amir M. Ghaemmaghami
The Journal of Immunology May 22, 2019, ji1801108; DOI: 10.4049/jimmunol.1801108

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The Cross-Talk between miR-511-3p and C-Type Lectin Receptors on Dendritic Cells Affects Dendritic Cell Function
Dennis Awuah, Meshal Alobaid, Arsalan Latif, Fabián Salazar, Richard D. Emes, Amir M. Ghaemmaghami
The Journal of Immunology May 22, 2019, ji1801108; DOI: 10.4049/jimmunol.1801108
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