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The cross-talk between miR-511-3p and c-type lectin receptors on dendritic cells affects dendritic cell function

Awuah, Dennis; Alobaid, Meshal; Latif, Arsalan; Salazar, Fabián; Emes, Richard D.; Ghaemmaghami, Amir M.

Authors

Dennis Awuah

Meshal Alobaid

Arsalan Latif

Fabián Salazar

RICHARD EMES richard.emes@nottingham.ac.uk
Professor of Bioinformatics



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.

Journal Article Type Article
Publication Date Jul 1, 2019
Journal Journal of Immunology
Print ISSN 0022-1767
Electronic ISSN 1550-6606
Publisher American Association of Immunologists
Peer Reviewed Peer Reviewed
Volume 203
Issue 1
Pages 148-157
APA6 Citation Awuah, D., Alobaid, M., Latif, A., Salazar, F., Emes, R. D., & Ghaemmaghami, A. M. (2019). The cross-talk between miR-511-3p and c-type lectin receptors on dendritic cells affects dendritic cell function. Journal of Immunology, 203(1), 148-157. doi:10.4049/jimmunol.1801108
DOI https://doi.org/10.4049/jimmunol.1801108
Publisher URL https://www.jimmunol.org/content/203/1/148