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.
RICHARD EMES firstname.lastname@example.org
Professor of Bioinformatics
Professor AMIR GHAEMMAGHAMI AMIR.GHAEMMAGHAMI@NOTTINGHAM.AC.UK
Professor of Immunology and Immuno-Bioengineering
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|
|Publisher||American Association of Immunologists|
|Peer Reviewed||Peer Reviewed|
|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|
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